p-Synephrine Indicates Internal Maturity of Citrus grandis (L.) Osbeck cv. Mato Peiyu-Reclaiming Functional Constituents from Nonedible Parts.

The processing of Citrus grandis Osbeck cv. Mato Peiyu (CGMP) fruits generates a considerable amount of waste, mainly the flavedo, albedo, and segment membrane; the generated waste yields severe environmental and economic challenges. In this study, we tried to reclaim some functional chemicals from the waste. Our data indicated that the essential oil content in the flavedo was 0.76-1.34%, with the major component being monoterpenes (93.75% in August, declining to 85.56% in November, including mainly limonene (87.08% to 81.12%) and others such as ß-myrcene). p-Synephrine (mg/100 g dry weight) declined accordingly (flavedo, 10.40 to 2.00; albedo, 1.80 to 0.25; segment membrane, 0.3 in August, 0.2 in September, and none since October). Polyphenols (in µg/g) included gallic acid (70.32-110.25, 99.27-252.89, and 105.78-187.36, respectively); protocatechuic acid (65.32-204.94, 26.35-72.35, and 214.98-302.65, respectively), p-coumaric acid (30.63-169.13, 4.32-17.00, and 6.68-34.32, respectively), ferulic acid (12.36-39.36, 1.21-10.25, and 17.07-39.63, respectively), and chlorogenic acid (59.19-199.36, 33.08-108.57, and 65.32-150.14, respectively). Flavonoids (in µg/g) included naringin (flavedo, 89.32-283.19), quercetin (181.05-248.51), nobiletin (259.75-563.7), hesperidin, and diosmin. The phytosterol content (mg/100 g) was 12.50-44.00 in the flavedo. The total dietary fiber in the segment membrane was 57 g/100 g. The antioxidant activity against the DPPH• and ABTS+• free radicals was moderately high. In conclusion, the waste of CGMP fruits is worth reclaiming for essential oil, p-synephrine, polyphenolics, and dietary fiber. Notably, p-synephrine content (flavedo: <8 mg/100 g dry weight, albedo: <2.0, or segment membrane: <0.4 mg) can serve as a marker of the internal maturation of CGMP fruits.

Potential Protection Effect of ER Homeostasis of N6-(2-Hydroxyethyl)adenosine Isolated from Cordyceps cicadae in Nonsteroidal Anti-Inflammatory Drug-Stimulated Human Proximal Tubular Cells.

Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to a class of universally and commonly used anti-inflammatory analgesics worldwide. A diversity of drawbacks of NSAIDs have been reported including cellular oxidative stress, which in turn triggers the accumulation of unfolded proteins, enhancing endoplasmic reticulum stress, and finally resulting in renal cell damage. Cordyceps cicadae (CC) has been used as a traditional medicine for improving renal function via its anti-inflammatory effects. N6-(2-hydroxyethyl)adenosine (HEA), a physiologically active compound, has been reported from CC mycelia (CCM) with anti-inflammatory effects. We hypothesize that HEA could protect human proximal tubular cells (HK-2) from NSAID-mediated effects on differential gene expression at the mRNA and protein levels. To verify this, we first isolated HEA from CCM using Sephadex® LH-20 column chromatography. The MTT assay revealed HEA to be nontoxic up to 100 µM toward HK-2 cells. The HK-2 cells were pretreated with HEA (10-20 µM) and then insulted with the NSAIDs diclofenac (DCF, 200 µM) and meloxicam (MXC, 400 µM) for 24 h. HEA (20 µM) effectively prevented ER stress by attenuating ROS production (p < 0.001) and gene expression of ATF-6, PERK, IRE1α, CDCFHOP, IL1ß, and NFκB within 24 h. Moreover, HEA reversed the increase of GRP78 and CHOP protein expression levels induced by DCF and MXC, and restored the ER homeostasis. These results demonstrated that HEA treatments effectively protect against DCF- and MXC-induced ER stress damage in human proximal tubular cells through regulation of the GRP78/ATF6/PERK/IRE1α/CHOP pathway.

Antihyperlipidemic bioactivity of Alpinia officinarum (Hance) Farw Zingiberaceae can be attributed to the coexistance of curcumin, polyphenolics, dietary fibers and phytosterols.

Rhizoma A. officinarum (Hance) Farw, synonymously is called rhizoma galangae or smaller galangal (hereafter abbreviated as AO). Numerous studies reported that AO possesses anti-inflammatory, anticancer, chemoprotective, antibacterial, antifungal and diuretic properties. To understand whether AO exhibits antihyperlipidemic bioactivity and what is the mechanism of action, we performed chemical and animal studies using hamsters (age: 4 weeks, body weight: 45 ± 4 g). The grouping of the animals was as follows: control, high fat (HF) diet, HF + AO2%, HF + AO4%, HF + AO6%, HF + AO8% and HF + AO10%. AO contained curcumin 5.67 mg g(-1) (on wet basis), crude fiber 1.3% ± 0.0%, soluble diet fiber 92 ± 2 mg g(-1), insoluble diet fiber 502 ± 5 mg g(-1), and phytosterols 63.9 ± 1.6 mg/100 g. Its methanolic extract consisted of high polyphenolics 4927.8 ± 101.1 mgGAE/100 g and flavonoids 593.2 ± 22.2 mgQE/100 g. The enlarged organs, including liver, kidney, and spleen, which were elicited by HF were completely alleviated by AO supplement diets. Levels of serum cholesterol, triglyceride, LDL-C, HDL-C and LDL-C/HDL-C ratio for the control originally were 138 ± 6, 98 ± 4, 40 ± 5, 168 ± 7 mg dL(-1) and 0.24, which were elevated by HF to 319 ± 12, 223 ± 13, 108 ± 11, 194 ± 6 mg dL(-1) and 0.05, and alleviated completely by HF + AO8% and HF + AO10%. In vitro, AO extracts showed potent DPPH free radical-scavenging and superoxide anion scavenging capabilities. In vivo, AO (at dose ≥8%) dose-dependently alleviated levels of superoxide dismutase, catalase, GSH, and MDA to 117 ± 6.9 U mL(-1), 32.9 ± 3.7 U mL(-1), 7.0 ± 1.7 µmol mL(-1) and 1.8 ± 0.4 nmol L(-1), respectively, exhibiting the remarkable antioxidative and antihyperlipidemic effects of AO. Conclusively, we are the first to report the occurrence of curcumin in rhizoma A. officinarum. Curcumin synergistically elicits promising anti-dyslipidemic bioactivity with coexisting total polyphenolics, dietary fibers and phytosterols.

Antrodan, a ß-glucan obtained from Antrodia cinnamomea mycelia, is beneficial to benign prostate hyperplasia.

Benign prostatic hyperplasia (BPH), one of the most common disease usually occurring in men in their 50s, has now become an atypical direct cause of mortality. Currently, phytotherapeutic agents are emerging and are frequently used as a complementary alternative treatment of BPH. ß-glucan has shown a diversity of bioactivities involving anticancer, immunomodulatory and anti-inflammatory effects. Antrodia cinnamomea exhibits a diversity of biological activities. Only a few literature references have cited the biomedicinal effects of antrodan, which is a unique ß-glucan present in A. cinnamomea mycelia. We hypothesized that antrodan could be beneficial to BPH. Using the Sprague-Dawley rat model, we performed this present experiment. Results indicated that antrodan alleviated most of the pathophysiological manifestations that can be elicited by BPH, by alleviating the prostatic epithelial hyperplasia and collagen deposition, increasing the total cholesterol biosynthesis and conversion into HDL, and suppressing the production of LDL and ROS and the upregulation of IL-1, COX-2 and CD68. Antrodan also effectively suppressed the serum level testosterone and DHT and downregulated aromatase, estradiol and the expression of the androgen receptor. More importantly, antrodan downregulated N-cadherin and vimentin and upregulated E-cadherin, underlying the effective inhibition on the epithelial-mesenchymal transition (EMT). Conclusively, the ß-glucan antrodan present in the A. cinamomea mycelia is beneficial to the BPH therapy.

Gallic acid exhibits risks of inducing muscular hemorrhagic liposis and cerebral hemorrhage--its action mechanism and preventive strategy.

Gallic acid (3,4,5-trihydroxybenzoic acid) (GA) occurs in many plants. The adverse effects of GA are seldom cited. GA (6-14 µM) provoked the hemorrhagic liposis of the cervical muscles and intracranial hemorrhage. The cause of these pathological events and the method for prevention are still lacking. Using the chicken embryo model and some selected nutraceutics such as folate, glutathione (GSH), N-acetylcysteine, and vitamin E (Vit E), we carried out this study. Results revealed that the action mechanism of GA involved (i) inducing hypoxia with upregulated gene hif-1α and downregulated ratio vegf-r2/vegf-a, leading to dys-vascularization and myopathy; (ii) impairing cytochrome c oxidase; (iii) stimulating creatine kinase and lactate dehydrogenase release; (iv) eliciting carnitine accumulation and liposis via downregulating gene CPT1; (v) suppressing superoxide dismutase and stimulating NO, H2O2, and malondialdehyde; and (vi) depleting erythrocytic and tissue GSH, resulting in hemorrhage. When both Vit E and GSH were applied to the day 1 chicks, a better alleviation effect was revealed. Conclusively, GA potentially exhibits adverse effect by eliciting hemorrhagic liposis of cervical muscles and cerebral hemorrhage. Supplementation with GSH, Vit E, and N-acetylcysteine is able to ameliorate these adverse effects, warranting the importance of restricting the clinical phytotherapeutic doses of GA and related compounds.

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".

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 × 10(4) cells/ µ L); RBC (5.30, 6.38, and 6.26 × 10(6) cells/ µ L); the platelet count (15.1, 12.8, and 11.3 × 10(5)/ µ L); 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.

Action Mechanism of Ginkgo biloba Leaf Extract Intervened by Exercise Therapy in Treatment of Benign Prostate Hyperplasia.

Benign prostatic hyperplasia (BPH), an imbalance between androgen/estrogen, overexpression of stromal, and epithelial growth factors associated with chronic inflammation, has become an atypical direct cause of mortality of aged male diseases. Ginkgo possesses anti-inflammatory, blood flow-enhancing, and free radical scavenging effects. Considering strenuous exercise can reduce BPH risks, we hypothesize Ginkgo + exercise (Ginkgo + Ex) could be beneficial to BPH. To verify this, rat BPH model was induced by s.c. 3.5 mg testosterone (T) and 0.1 mg estradiol (E2) per head per day successively for 8 weeks, using mineral oil as placebo. Cerenin(®) 8.33 µ L/100 g was applied s.c. from the 10th to the 13th week, and simultaneously, Ex was applied (30 m/min, 3 times/week). In BPH, Ginkgo alone had no effect on T, 5 α -reductase, and dihydrotestosterone (DHT), but suppressed androgen receptor (AR), aromatase, E2 and estrogen receptor (ER), and the proliferating cell nuclear antigen (PCNA); Ex alone significantly reduced T, aromatase, E2, ER, AR, and PCNA, but highly raised DHT. While Ginkgo + Ex androgenically downregulated T, aromatase, E2, and ER, but upregulated DHT, AR, and PCNA, implying Ginkgo + Ex tended to worsen BPH. Conclusively, Ginkgo or Ex alone may be more beneficial than Ginkgo + Ex for treatment of BPH.

Extraction of antioxidant components from Bidens pilosa flowers and their uptake by human intestinal Caco-2 cells.

Bidens pilosa L. var. radiata (BPR, Asteraceae) is a commonly used folk medicine for treating various disorders such as diabetes, inflammation and hypertension. Recent studies to determine its chemical composition have revealed three di-O-caffeoylquinic acids (DiCQAs) and three polyacetylene glucosides (PGAs) to be among the major bioactive markers. To obtain the major compounds of these two chemical classes, the ethyl acetate fraction (EM) obtained using liquid-liquid partition from the methanol extract resulted in a fraction with the highest total phenolic and total flavonoid contents and antioxidant activities in radical scavenging and ferric reducing power assays. To assess the bioavailability of EM, we examined the in vitro uptake using the Caco-2 human colonic cell line. The apparent permeability coefficient (Papp) for each of the compounds within PGAs measured in both apical (AP) to basolateral (BL) and BL to AP was found to preferentially appear BL to AP direction, indicated that a basolateral to apical efflux system was detected in the study. DiCQAs had a lower efflux ratio than those from PGAs (2.32-3.67 vs. 6.03-78.36). Thus, it strongly implies that most of the DiCQAs are better absorbed than the PGAs.

Unique bioactive polyphenolic profile of guava (Psidium guajava) budding leaf tea is related to plant biochemistry of budding leaves in early dawn.

BACKGROUND: Guava leaf tea (GLT), exhibiting a diversity of medicinal bioactivities, has become a popularly consumed daily beverage. To improve the product quality, a new process was recommended to the Ser-Tou Farmers' Association (SFA), who began field production in 2005. The new process comprised simplified steps: one bud-two leaves were plucked at 3:00-6:00 am, in the early dawn period, followed by withering at ambient temperature (25-28 °C), rolling at 50 °C for 50-70 min, with or without fermentation, then drying at 45-50 °C for 70-90 min, and finally sorted. RESULTS: The product manufactured by this new process (named herein GLTSF) exhibited higher contents (in mg g(-1), based on dry ethyl acetate fraction/methanolic extract) of polyphenolics (417.9 ± 12.3) and flavonoids (452.5 ± 32.3) containing a compositional profile much simpler than previously found: total quercetins (190.3 ± 9.1), total myricetin (3.3 ± 0.9), total catechins (36.4 ± 5.3), gallic acid (8.8 ± 0.6), ellagic acid (39.1 ± 6.4) and tannins (2.5 ± 9.1). CONCLUSION: We have successfully developed a new process for manufacturing GLTSF with a unique polyphenolic profile. Such characteristic compositional distribution can be ascribed to the right harvesting hour in the early dawn and appropriate treatment process at low temperature, avoiding direct sunlight.

Antrodia cinnamomea exhibits a potent neuroprotective effect in the PC12 Cell-Aß25-35 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 Aß25-35. 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 Aß25-35 (15 µM), the cell viability was suppressed in a dose-dependent fashion with an IC50 value of 10 µM. The biochemical parameters upregulated by Aß25-35 (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 Aß25-35 downregulated BcL-2/Bax and upregulated cleaved caspases-9 and - 3 without affecting cleaved caspase-8. The G2/M arrest elicited by Aß25-35 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, Aß25-35 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.

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.

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-ß; and down-regulated p-PI3K, and p-Akt. Since both PDGF-BB and TGF-ß 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.

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 lowdensity 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.

The Aqueous Soluble Polyphenolic Fraction of Psidium guajava Leaves Exhibits Potent Anti-Angiogenesis and Anti-Migration Actions on DU145 Cells.

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.

Structural Characteristics and Antioxidative Capability of the Soluble Polysaccharides Present in Dictyophora indusiata (Vent. Ex Pers.) Fish Phallaceae.

Dictyophora indusiata (Vent. ex Pers.) Fish Phallaceae (Chinese name Zhu-Sun, the bamboo fungi) has been used as a medicinal mushroom to treat many inflammatory, gastric and neural diseases since 618 AD in China. We hypothesize that the soluble polysaccharides (SP) present in D. indusiata and their monosaccharide profiles can act as an important role affecting the antioxidative capability, which in turn would influence the biological activity involving anti-inflammatory, immune enhancing and anticancer. We obtained six SP fractions and designated them as D1, a galactoglucan; D2, a galactan; D3, the isoelectrically precipitated riboglucan from 2% NaOH; D4, a myoinositol; D5 and D6, the mannogalactans. The total SP accounted for 37.44% w/w, their molecular weight (MW) ranged within 801-4656 kDa. D3, having the smallest MW 801 kDa, exhibited the most potent scavenging effect against the α,α-diphenyl-ß-picrylhydrazyl, •OH(-), and •O(2) (-) radicals, yielding IC(50) values 0.11, 1.02 and 0.64 mg mL(-1), respectively. Thus we have confirmed our hypothesis that the bioactivity of D. indusiata is related in majority, if not entirely, to its soluble polysaccharide type regarding the MW and monosaccharide profiles.

Fermented soybean liquid alleviated peptic ulcer through the destruction of acidic proton pump rather than suppression of urease of Helicobacter pylori: a kinetic analysis.

Fermented soybean liquid (FSL) has been well cited for its broad spectrum of biological effects, yet its documented gastropeptic ulcer (GPU) ameliorating effect is still lacking. It was hypothesized that to avoid the injury exerted by gastric fluid, HP has to be sheltered in chyme emulsions immediately on infection. The HP urease (HPU) and the acidic proton pump (PP) may act as the "two-point pH modulator" to maintain an optimum pH between 6 and 7, and FSL is able to destroy such a modulating mechanism. FSL exhibited higher contents of isoflavonoids (2.5-17.3-fold) and essential amino acids (1.5-4.0-fold) than the nonfermented. FSL administered at 1 g/20 mL tid for 3 months eradicated Helicobacter pylori (HP) by 82% in 37 volunteers having GPU (p < 0.20); simultaneously, the plasma conjugated diene and TBARs levels were significantly resumed (p < 0.05). Kinetic analysis based on the conventional "urease theory" revealed that a cluster of 2.0 × 10(9) of HP cells is required for a single attack in the gastric lumen at pH 1.0-2.5. To verify the hypothesis, chyme-shelter testing was conducted in artificial gastric fluid (pH 2.4 ± 0.20). Results showed the HP cell viability was time- and size-dependent. At 20 min of contact time, the viability was 100, 4.2, 31.4, 43.3, 57.2, and 82.6%, respectively, in intact, dispersed, and particulate chymes (mesh sizes 80, 60, 40, and 20). The corresponding data became 96.2, 0.0, 14.5, 18.5, 21.3, and 28.6%, respectively, at a contact time of 40 min. Conclusively, the kinetic analysis and the chyme-shelter testing revealed that direct infection by bare HP cells is unlikely in real status. FSL is beneficial to GPU most probably due to its ability to raise blood alkalinity levels, destroying the PP and its ROS suppressing effect.

Anti-inflammatory effects of supercritical carbon dioxide extract and its isolated carnosic acid from Rosmarinus officinalis leaves.

Rosemary (Rosmarinus officinalis) leaves possess a variety of bioactivities. Previous studies have shown that the extract of rosemary leaves from supercritical fluid extraction inhibits the expression of inflammatory mediators with apparent dose-dependent responses. In this study, three different extraction conditions (5000 psi at 40, 60, and 80 °C) of supercritical carbon dioxide (SC-CO(2)) toward the extraction of antioxidants from rosemary were investigated. Furthermore, simultaneous comparison of the anti-inflammatory properties between rosemary extract prepared from SC-CO(2) under optimal conditions (5,000 psi and 80 °C) and its purified carnosic acid (CA) using lipopolysaccharide (LPS)-treated murine RAW 264.7 macrophage cells was also presented. Results showed that the yield of 3.92% and total phenolics of 213.5 mg/g extract obtained from the most effective extraction conditions showed a high inhibitory effect on lipid peroxidation (IC(50) 33.4 µg/mL). Both the SC-CO(2) extract and CA markedly suppressed the LPS-induced production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), phosphorylated inhibitor-kappaB (P-IκB), and nuclear factor-kappaB (NF-κB)/p65 in a dose-dependent manner. The five major compounds of verbenone, cirsimaritin, salvigenin, carnosol, and CA existing in the SC-CO(2) extract were isolated by semipreparative HPLC and identified by HPLC-MS/MS analysis. CA was the most abundant recorded compound and the most important photochemical with an anti-inflammatory effect with an IC(50) of 22.5 µM or 7.47 µg/mL presented to the best inhibitory activity on NO production better than that of the 14.50 µg/mL dosage prepared from the SC-CO(2) extract. Nevertheless, the effective inhibition of LPS-induced NF-κB signaling in RAW 264.7 cells from the SC-CO(2) extract extends the potential application of nutraceutical formulation for the prevention of inflammatory diseases.

Action mechanism and signal pathways of Psidium guajava L. aqueous extract in killing prostate cancer LNCaP cells.

Aqueous extract of Psidium guajava L. budding leaves (PE) has been shown to possess anti-prostate cancer activity in a cell line model. We examined whether its bioactivity could be conserved either in the presence or the absence of synthetic androgen R1881. In both cases, PE was shown to inhibit LNCaP cell proliferation and down-regulate expressions of androgen receptor (AR) and prostate specific antigen (PSA). The cytotoxicity of PE was shown by enhanced LDH release in LNCaP cells. The flow cytometry analysis revealed cell cycle arrests at G(0)/G(1) phase with huge amount of apoptotic LNCaP cells after treatment with PE for 48 h in a dose-responsive manner, which was also confirmed by TUNEL assay. From the results of decreased Bcl-2/Bax ratio, inactivation of phosphor-Akt, activation of phosphor-p38, phospho-Erk1/phospho-Erk2, the molecular action mechanism of PE to induce apoptosis in LNCaP cells was elucidated. Compatible with the in vitro study findings, treatment with PE (1.5 mg/mouse/day) significantly diminished both the PSA serum levels and tumor size in a xenograft mouse tumor model. Conclusively, PE is a promising anti-androgen-sensative prostate cancer agent.

Pivotal role of curcuminoids on the antimutagenic activity of Curcuma zedoaria extracts.

In an investigation of the mutagenic activity of two extracts from rhizomes of Curcuma zedoaria (the mathanolic, CME, and the aqueous, CAE) and antimutagenic activity against mutagens, either 2-amino-3-methylimidazo (4,5-f) quinoline (IQ) or 4-nitroquinoline-N-oxide (4-NQO), in dosages of 1-50 microg/plate was assayed by using Salmonella typhimurium TA97, TA98, TA100, and TA102 strains. We found that the two extracts showed no mutagenicity when tested with all the tester strains either with or without the S9 mix. Moreover, the two extracts, particularly CME, presented a greater antimutagenicity than CAE did either in IQ or 4-NQO mutagens. However, the inhibition effect on lipid peroxidation was similar with both extracts. The amount of major antioxidants beta-carotene, ascorbic acid, and total polyphenols present in both CME and CAE were similar between each other. In contrast, the content of cucuminoids (44.3 mg/g extract) in CME were only found in small amounts in CAE (0.09 mg/g extract). Consequently, although both of the extracts showed similar antioxidant effects, the curcuminoids, which seem to be the main active principles from this plant, were suggested to play a pivotal role in antimutagenic activity.