Yaw Bee Ker

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.

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.

Hepatoprotective bioactivity of the glycoprotein, antrodan, isolated from Antrodia cinnamomea mycelia

Antrodan, a protein-bound polysaccharide isolated from Antrodia cinnamomea mycelia, was demonstrated to exhibit significant anti-inflammatory bioactivity in vitro. However, its role in hepatic injury in vivo still remains unclear. We hypothesized that antrodan may have beneficial hepatoprotective effects. To verify this, a lipopolysaccharide (LPS)-Sprague-Dawley rat model was used. Antrodan protected against liver damage by suppressing LPS-stimulated serum glutamine-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), interleukin (IL)-6, hepatic thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), inducible NO synthase (iNOS) and nuclear factor (NF)-κB, and by effectively alleviating the downregulated hepatic superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px). Hematoxylin-eosin staining revealed that antrodan at a dosage of 40 mg/kg was able to alleviate LPS-induced liver damage to a normal status. In addition, we identified the partial main architectural backbone of antrodan to have a 1→3 linear β-glycosidic backbone of mannan linked by β-1→3 glucosidic branches. Conclusively, antrodan can potentially ameliorate liver damage in vivo by suppressing oxidative stress induced by LPS.

Physicochemical Characteristics and Anti-Inflammatory Activities of Antrodan, a Novel Glycoprotein Isolated from Antrodia cinnamomea Mycelia

Antrodia cinnamomea (AC) is a unique fungus found inhabiting the rotten wood of Cinnamomum kanehirai. A submerged liquid culture of AC has been developed and its bioproducts have been used to meet the market demand for natural fruiting bodies. AC exhibits anti-inflammatory, antitumor, antioxidant, and immunomodulatory effects. Previously, we isolated polysaccharide AC-2 from AC mycelia by means of alkali extraction with subsequent acid precipitation and found it had a pronounced anti-inflammatory effect. In this study, a novel polysaccharide named “antrodan” was obtained by further purification of AC-2 using Sepharose CL-6B column chromatography. Antrodan exhibited a molecular weight of 442 kD and contained a particularly high content of uronic acid (152.6 ± 0.8 mg/g). The protein content was 71.0%, apparently, higher than the carbohydrate content (14.1%), and thus antrodan was characterized as a glycoprotein. Its total glucan content was 15.65%, in which β-glucan (14.20%) was prominently higher than α-glucan (1.45%). Its FTIR confirmed the presence of β-linkages between sugars, and intramolecular amide bonds between sugars and amino acids. Its 1H-NMR spectrum showed that antrodan was a complex union of α- and β-glucans, which had (1→4)-linked α-Glcp and (1→3)-linked β-Glcp linkages to the carbohydrate chains via asparagine linked to protein site. Biologically, antrodan was confirmed to be totally non-detrimental to RAW 264.7 cell line even at dose as high as 400 μg/mL. It showed potent suppressing effect on the lipopolysaccharide-induced inflammatory responses in RAW 264.7 cell line. Moreover, antrodan significantly reduced the nitrogen oxide production at doses as low as 18.75 μg/mL.

Selected nutraceutic screening by therapeutic effects on doxorubicin-induced chronic kidney disease

SCOPE The number of patients with chronic kidney disease (CKD) are increasing. Interventions such as controlling hypertension and specific pharmacologic options are recommended. Some nutraceutics may have benefits in this regard. METHODS AND RESULTS Naringenin (a flavanon), catechin (a flavanol), and quercetin (a flavonol) and rutin (a flavonol rutinoside) were tried on CKD in a Sprague Dawley rat model. Results indicated quercetin to be the most effective therapeutic candidate with respect to renal edema, hypertension, serum creatinine, hematocrit, cardiopathy, aorta calcification, glomerular amyloidosis, erythrocyte depletion in bone marrow, collagen deposition, expressions of TNF-α, cleaved caspase-3, IκBα, PPARα, and serum insulin. But quercetin was only partially effective in restoring glomerular filtration rate, albuminuria, serum cholesterol, triglyceride, blood urea nitrogen (BUN), uric acid, malondialdehyde, superoxide dismutase; urinary BUN and urinary creatinine. As for signaling, quercetin was completely effective in alleviating the cleaved caspase-3, being only partially effective in suppressing Bax and Bad, restoring Bcl-2, and rescuing DNA damage. CONCLUSION The CKD status cannot to be ameliorated by naringenin, rutin, and catechin. Comparatively, quercetin may be a better therapeutic candidate.

Arabinogalactan present in the mountain celery seed extract potentiated hypolipidemic bioactivity of coexisting polyphenols in hamsters

Context: Previously, we showed the essential oils (EO) of the mountain celery [Cryptotaenia japonica Hass (Umbelliferae)] seeds (MCS) to be a prominent hypolipidemic agent. Objective: We hypothesized the aqueous extract (AE) of its seeds could also exhibit a comparable nutritional effect. Materials and methods: Experiments were carried out for compositional analysis, antioxidant assay, and hypolipidaemic assay with AE in hamsters. Results: AE contained soluble arabinogalactan (AGal) with molecular weight (MW) 878 kDa. AE also was enriched in polyphenolics and flavonoids, reaching 30.4 and 2.20 mg/100 g, respectively. AGal consisted of eight monosaccharides (in mols %), galactose (28.75), arabinose (24.84), glucose (17.91), mannose (6.93), ribose (6.03), fucose (5.83), xylose (5.30), and rhamnose (4.41), with average MW 878 kDa. In vitro, AE showed potent ferrous chelating and DPPH scavenging effects but only moderate H2O2 scavenging capability. In hamsters, AE exhibited promising hypolipidemic bioactivity, in particular, the HDL-C and hepatic unsaturated fatty acid (UFA) biosynthesis regarding oleic, linoleic, and arachidonic acids. Discussion and conclusion: The presence of AGal enhanced the hypolipidemic and antioxidative bioactivity of MCS. MCS is feasibly beneficial to the hepatic de novo UFA synthesis and the hypolipidemics as evidenced by hamster model.

In Vitro Polyphenolics Erythrocyte Model and in Vivo Chicken Embryo Model Revealed Gallic Acid to Be a Potential Hemorrhage Inducer: Physicochemical Action Mechanisms

The in vivo chicken embryo model (CEM) demonstrated that gallic acid (GA) induced dysvascularization and hypoxia. Inflammatory edema, Zenkers necrosis, hemolysis, and liposis of cervical muscles were the common symptoms. Levels of the gene hif-1α, HIF-1α, TNF-α, IL-6, and NFκB in cervical muscles were all significantly upregulated, while the vascular endothelial growth factor (VEGF) was downregulated in a dose-responsive manner. Consequently, the cervical muscle inflammation and hemolysis could have been stimulated en route to the tissue TNF-α-canonical and the atypical pathways. We hypothesized that GA could deplete the dissolved oxygen (DO) at the expense of semiquinone and quinone formation, favoring the reactive oxygen species (ROS) production to induce RBC disruption and Fe(2+) ion release. To explore this, the in vitro polyphenolics-erythrocyte model (PEM) was established. PEM revealed that the DO was rapidly depleted, leading to the release of a huge amount of Fe (II) ions and hydrogen peroxide (HPO) in a two-phase kinetic pattern. The kinetic coefficients for Fe (II) ion release ranged from 0.347 h(-1) to 0.774 h(-1); and those for Fe (III) ion production were from 6.66 × 10(-3) h(-1) to 8.93 × 10(-3) h(-1). For phase I HPO production, they ranged from 0.236 h(-1) to 0.774 h(-1) and for phase II HPO production from 0.764 h(-1) to 2.560 h(-1) at GA within 6 μM to 14 μM. Thus, evidence obtained from PEM could strongly support the phenomena of CEM. To conclude, GA tends to elicit hypoxia-related inflammation and hemolysis in chicken cervical muscles through its extremely high prooxidant activity.

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”.

Sacchachitin, a novel chitin-polysaccharide conjugate macromolecule present in Ganoderma lucidum: Purification, composition, and properties

Context: The extraction method and the crude wound healing effects of sacchachitin from Ganoderma tsugae Murr. (Ganodermataceae) has been cited. However, its purity is still largely limited. Objective: An improvement of the fractionation protocol to purify the sacchachitin from Ganoderma lucidum L. (Ganodermataceae) (SGL) is needed. Methods: Fruiting bodies were extracted with double distilled water and subsequently the residue treated with 95% ethanol and then 40% ethanol. After being filtered, the pH of the supernatant was adjusted to 4.0 with 1 N HCl and lyophilized. The supernatant was added (3:1 v/v) ethanol, the precipitate was collected, 2% NaOH was added and refluxed. The supernatant was collected with pH adjusted to 4.0, then treated with 10% potassium hydroxide (KOH) with repeating acid precipitation and (3:1) ethanol precipitation twice more to obtain the sacchachitin. Results: SGL had a hexosamine content 16.3% (w/w), firmly linked to a talomannan. Its Fourier Transform Infrared Spectroscopy (FTIR) spectrum revealed specific absorption (in cm–1) νO–H 3455.5 b,s, amide νC=O 1678.5, and amide I° δN–H 1550.4. The percentage deacetylation degree was 37.6 and 39.4% for SGL and MSC, respectively. As contrast, MSC contained only 6.6% of hexosamine with a low protein/carbohydrate ratio 0.35 comparing to 0.82 for SGL. SGL was only moderately strong antioxidant regarding the anti-DPPH, antihydroxyl free radical, and antisuperoxide anion capabilities, exhibiting an IC33 values of 10 mg/mL (the highest scavenging capability never exceeding 33%), 0.9 mg/mL, and 4.8 mg/mL, respectively. Conclusion: We have successfully isolated the pure sacchachitin from the fruiting bodies of G. lucidum that exhibits potent antioxidative activity and may be useful in fabrication of the artificial skin composite substitute.

Feasibility of pressure swing adsorption (PSA) plus thermal swing adsorption (TSA) technology for odorant separation - A process design approach

Abstract PSA (pressure swing adsorption) has been a well known commercialized process in the petroleum refining engineering. With the consideration that the volatiles, odorants or essential oils in a variety of plants and herbs may be separated taking the advantage of PSA, we present in this article a newly designed process: PSA plus TSA (thermal swing adsorption). As the odorants or essential oils are unlike the volatile components in the petroleum, being characteristic with higher boiling points and able to become liquefied during the PSA treatment, thereby a TSA technique is necessarily incorporated, so that the whole process can be operated in an entirely gaseous phase to facilitate the separation.