Shylaja M. Dharmesh

Gastroprotective Effect of Ginger Rhizome (Zingiber officinale) Extract: Role of Gallic Acid and Cinnamic Acid in H(+), K(+)-ATPase/H. pylori Inhibition and Anti-Oxidative Mechanism.

Zinger officinale has been used as a traditional source against gastric disturbances from time immemorial. The ulcer-preventive properties of aqueous extract of ginger rhizome (GRAE) belonging to the family Zingiberaceae is reported in the present study. GRAE at 200 mg kg−1 b.w. protected up to 86% and 77% for the swim stress-/ethanol stress-induced ulcers with an ulcer index (UI) of 50 ± 4.0/46 ± 4.0, respectively, similar to that of lansoprazole (80%) at 30 mg kg−1 b.w. Increased H+, K+-ATPase activity and thiobarbituric acid reactive substances (TBARS) were observed in ulcer-induced rats, while GRAE fed rats showed normalized levels and GRAE also normalized depleted/amplified anti-oxidant enzymes in swim stress and ethanol stress-induced animals. Gastric mucin damage was recovered up to 77% and 74% in swim stress and ethanol stress, respectively after GRAE treatment. GRAE also inhibited the growth of H. pylori with MIC of 300 ± 38 μg and also possessed reducing power, free radical scavenging ability with an IC50 of 6.8 ± 0.4 μg mL−1 gallic acid equivalent (GAE). DNA protection up to 90% at 0.4 μg was also observed. Toxicity studies indicated no lethal effects in rats fed up to 5 g kg−1 b.w. Compositional analysis favored by determination of the efficacy of individual phenolic acids towards their potential ulcer-preventive ability revealed that between cinnamic (50%) and gallic (46%) phenolic acids, cinnamic acid appear to contribute to better H+, K+-ATPase and Helicobacter pylori inhibitory activity, while gallic acid contributes significantly to anti-oxidant activity.

Ulcer preventive and antioxidative properties of astaxanthin from Haematococcus pluvialis.

The anti-ulcer properties of astaxanthin fractions such as total carotenoid and astaxanthin esters from Haematococcus pluvialis were evaluated in ethanol-induced gastric ulcers in rats. Since oxygen radical release is a pathogenic factor of ethanol-induced gastric damage, astaxanthin - a free radical scavenger, was investigated as a potential ulcer preventive agent. Astaxanthin fractions - total carotenoid and astaxanthin esters were orally administered to experimental rats at 100, 250 and 500 microg/kg b.w. prior to ulcer induction. Alcian blue binding assay indicates that, total carotenoid and astaxanthin esters at 500 microg/kg b.w could protect gastric mucin approximately 40% and 67% respectively. Pre-treatment with astaxanthin esters, also resulted in significant increase in antioxidant enzyme levels - catalase, superoxide dismutase, and glutathione peroxidase in stomach homogenate. Histopathological examination substantiated the protective effect of astaxanthin in pre-treated rats. The increased antioxidant potencies such as free radical scavenging activity with an IC(50) of approximately 8 microg/ml and reducing power abilities (59 x 10(3) U/g) in vitro, reveal that H. pluvialis astaxanthin may protect gastric mucosal injury by antioxidative mechanism. In addition, approximately 23 fold increased lipoxygenase-inhibitory property, in comparison with standard astaxanthin and significant H(+), K(+)-ATPase-inhibitory activity of astaxanthin esters, in comparison with known proton pump blocking anti-ulcer drug - omeprazole, may envisage the potential gastroprotective effect by regulating the gastric mucosal injury and gastric acid secretion by the gastric cell during ulcer disease.

Effective inhibition of skin cancer, tyrosinase, and antioxidative properties by astaxanthin and astaxanthin esters from the green alga Haematococcus pluvialis.

Astaxanthin mono- (AXME) and diesters (AXDE) were characterized and examined for anticancer potency with total carotenoids (TC) and astaxanthin (AX) against UV-7,12-dimethylbenz(a)anthracene (DMBA)-induced skin cancer model in rat. At 200 μg/kg bw, AXDE and AXME reduced UV-DMBA-induced tumor incidences up to 96 and 88%, respectively, when compared to AX (66%) and TC (85%). UV-DMBA has been known to generate high levels of free radicals and tyrosinase enzyme, leading to characteristic symptoms of skin pigmentation and tumor initiation. Intriguingly, ~7-fold increase in tyrosinase and 10-fold decrease in antioxidant levels were normalized by AXDE and AXME as opposed to only ~1.4-2.2-fold by AX and TC, respectively. This result together with the appearance of 72 and 58 ng/mL of retinol in the serum of respective AXE-treated (AXDE + AXME) and AX-treated animals suggested that better anticancer potency of AXEs could be due to increased bioavailability.

Interaction of sesamol (3,4-methylenedioxyphenol) with tyrosinase and its effect on melanin synthesis

Sesamin, sesamolin (lignans) and sesamol--from sesame seed (Sesamum indicum L.)--are known for their health promoting properties. We examined the inhibition effect of sesamol, a phenolic degradation product of sesamolin, on the key enzyme in melanin synthesis, viz. tyrosinase, in vitro. Sesamol inhibits both diphenolase and monophenolase activities with midpoint concentrations of 1.9 μM and 3.2 μM, respectively. It is a competitive inhibitor of diphenolase activity with a K(i) of 0.57 μM and a non-competitive inhibitor of monophenolase activity with a K(i) of 1.4 μM. Sesamol inhibits melanin synthesis in mouse melanoma B16F10 cells in a concentration dependant manner with 63% decrease in cells exposed to 100 μg/mL sesamol. Apoptosis is induced by sesamol, limiting proliferation. This study of the chemistry and biology of lignans, in relation to the mode of action of bioactive components, may open the door for drug applications targeting enzymes.

Biodegradable Poly (Lactic‐co‐Glycolic Acid)–Polyethylene Glycol Nanocapsules: An Efficient Carrier for Improved Solubility, Bioavailability, and Anticancer Property of Lutein

Lutein bioavailability is limited because of its poor aqueous solubility. In this study, lutein-poly (lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG) nanocapsules were prepared to improve the solubility, bioavailability, and anticancer property of lutein. The scanning electron microscopy and dynamic light scattering examination revealed that the nanocapsules are smooth and spherical with size ranging from 80 to 500 nm (mean = 200 nm). In vitro lutein release profile from nanocapsules showed controlled sustainable release (66%) up to 72 h. Aqueous solubility of lutein nanocapsules was much higher by 735-fold than the lutein. Fourier transform infrared spectroscopy analyses showed no chemical interaction among PLGA, PEG, and lutein, indicating possible weak intermolecular forces like hydrogen bonds. X-ray diffraction revealed lutein is distributed in a disordered amorphous state in nanocapsules. Postprandial plasma kinetics (area under the curve) of an oral dose of lutein from nanocapsules was higher by 5.4-fold compared with that of micellar lutein (control). The antiproliferative effect of lutein from nanocapsules (IC50 value, 10.9 μM) was higher (43.6%) than the lutein (IC50 value, 25 μM). Results suggest that PLGA-PEG nanocapsule is an efficient carrier for enhancing hydrophilicity, bioavailability, and anticancer property of lipophilic molecules such as lutein.

Pectic polysaccharide from corn (Zea mays L.) effectively inhibited multi-step mediated cancer cell growth and metastasis

Corn pectic polysaccharide (COPP) inhibited galectin-3 mediated hemagglutination at Minimum Inhibitory Concentration (MIC) of 4.08 μg/mL as opposed to citrus pectin (25 μg/mL), a well known galectin-3 inhibitor and lactose (4.16 μg/mL)--sugar specific to galectin-3. COPP effectively (72%) inhibited invasion and metastasis in experimental animals. In vivo results were substantiated by modulation of cancer specific markers such as galectin-3, which is a key molecule for initiation of metastatic cascade, vascular endothelial growth factor (VEGF) that enhances angiogenesis, matrix metalloproteinases 2 and 9 that are required for invasion, NF-κB, a transcription factor for proliferative potency of tumor cells and a phosphoglucoisomerase (PGI), the activity of which favors cancer cell growth. Structural characterization studies indicate the active component (relatively less acidic, 0.05 M ammonium carbonate, 160 kDa fraction) which showed antimetastatic potency in vitro with MIC of 0.09 μg/mL, and ∼ 45 fold increase in the activity when compared to that of COPP. Gas liquid chromatographic analysis indicated the presence of rhamnose (1%), arabinose (20%), xylose (3%), mannose (4%), galactose (54%) and uronic acid (10%) in different proportions. However, correlative data attributed galectin-3 inhibitory activity to enhanced levels of arabinose and galactose. FTIR, HPLC and NMR spectroscopic analysis further highlights that COPP is an arabinogalactan with methyl/ethyl esters. It is therefore suggested that the blockade of galectin-3 mediated lung metastasis appears to be a result of an inhibition of mixed functions induced during metastasis. The data signifies the importance of dietary carbohydrate as cancer-preventive agent. Although pectin digestibility and absorption are issues of concern, promising in vivo data provides evidence for the cancer preventive property of corn. The present study reveals for the first time a new component of corn, i.e.,--corn pectin with cancer preventive activity apart from corn starch that has been in wide use for multipurpose health benefits.

Modified pectic polysaccharide from turmeric (Curcuma longa): A potent dietary component against gastric ulcer

Native, intact (TrPP) and modified, low-molecular-weight (MTrPP) forms of pectic polysaccharides isolated from turmeric were evaluated for ulcer-preventive potentials in in vitro and in vivo models. Data indicated that MTrPP possessed significantly better ulcer-preventive property than TrPP; inhibiting ulcer scores up to 85%. Results were substantiated by effective muco-protection, H(+),K(+)-ATPase down-regulation, inhibition of H. pylori growth/adherence, higher antioxidant/cytoprotective mechanisms. Structural data indicated TrPP and MTrPP differ in their molecular weights and structural characteristics with different sugar compositions and side chain ratios. MTrPP was rich in galacturonic acid (687mg/g; TrPP-544mg/g) and galactose (52.9%; TrPP-21.7%). Results were substantiated by NMR/FTIR data indicating the presence of homogalacturonan and rhamnogalacturonam-I containing galactans. By virtue of binding to inflammatory marker (galectin-3), galactans may reduce inflammation induced ulcerations. The low molecular weight of MTrPP (155kDa; TrPP-13kDa) may increase its bioavailability than TrPP, thus MTrPP may possess higher antiulcer potential.

Gastroprotective Properties of Karanjin from Karanja (Pongamia pinnata) Seeds; Role as Antioxidant and H, K-ATPase Inhibitor.

Plant extracts are the most attractive sources of newer drugs and have been shown to produce promising results for the treatment of gastric ulcers. Karanjin, a furano-flavonoid has been evaluated for anti-ulcerogenic property by employing adult male albino rats. Karanjin (>95% pure) was administered to these rats in two different concentrations, that is, 10 and 20 mg kg−1 b.w. Ulcers were induced in the experimental animals by swim and ethanol stress. Serum, stomach and liver-tissue homogenates were assessed for biochemical parameters. Karanjin inhibited 50 and 74% of ulcers induced by swim stress at 10 and 20 mg kg−1 b.w., respectively. Gastric mucin was protected up to 85% in case of swim stress, whereas only 47% mucin recovery was seen in ethanol stress induced ulcers. H+, K+-ATPase activity, which was increased 2-fold in ulcer conditions, was normalized by Karanjin in both swim/ethanol stress-induced ulcer models. Karanjin could inhibit oxidative stress as evidenced by the normalization of lipid peroxidation and antioxidant enzyme (i.e., catalase, peroxidase and superoxide dismutase) levels. Karanjin at concentrations of 20 mg kg−1 b.w., when administered orally for 14 days, did not indicate any lethal effects. There were no significant differences in total protein, serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase and alkaline phosphatase between normal and Karanjin-treated rats indicating no adverse effect on major organs. During treatment schedule, animals remained as healthy as control animals with normal food and water intake and body weight gain.

Assessment of antioxidant potentials of free and bound phenolics of Hemidesmus indicus (L) R.Br against oxidative damage.

Background: Hemidesmus indicus R.Br. is a twining shrub commonly found in India, which was known to have wide pharmacological actions. 2-hydroxy-4-methoxy-benzoic acid (HMBA) and a number of pregnane glycosides were believed to be responsible for its various bioactivities. Until now, there are no reports regarding the antioxidant properties of phenolics from H. indicus Objective: To establish the role of phenolics in the properties of H.indicus. Materials and Methods: Hemidesmus free phenolic fraction (HDFP) and Hemidesmus bound phenolic fraction (HDBP) have been isolated from H. indicus, and the antioxidant activity was evaluated for inhibition of lipid peroxidation, DNA protection, free radical scavenging (FRS), reducing power and cytoprotective activities. Results: HDFP and HDBP exhibited potent inhibition of lipid peroxidation (IC50 - 19.5 ±0.5 and 21.7 ±0.5 μg gallic acid equivalent - GAE/mL), FRS (IC50 - 7 ± 0.2 and 8.6 ± 0.2 μgGAE/mL), reducing power (110.3 ± 2 and 33.5 ± 1 U/g) and red blood cell protection (14.8 ± 0.4 and 14.5 ± 0.5 mg GAE/mL). HDFP is constituted by gallic (18%), caffeic (17%), ferulic acids (16%) and HDBP by syringic acid (35%) as major phenolic acids. Besides, both HDFP and HDBP contained significant levels of HMBA; in HDFP (10%) and HDBP (57%), respectively. Results indicated a 34-and 27-folds better contribution to the antioxidant activity by HDFP and HDBP, respectively, than that of HMBA. Conclusion: Potent antioxidant activities of phenolics may be one of the mechanisms by which H.indicus is effective against several health disorders as encountered in traditional medicines.

Gastro protective and H+, K+-ATPase/H. pylori inhibitory properties of pectic polysaccharides from potato

Polysaccharide is one among the important classes of biological polymers that is reported to exhibit disease preventive properties. The present study describes the isolation of galactans and confirmation of the same by sugar analysis and determination of anti-ulcer effect of Potato Galactan Polysaccharide (PGP). Data indicated that PGP possessed sugar composition of rhamnose (2%), arabinose (3%), mannose (3%), galactose (94%) and uronic acid (17%) confirming that PGP thus isolated is a galactan. PGP exhibited potent H(+), K(+)-ATPase inhibitory activity (IC50 420 μg/mL) in vitro as opposed to lansoprazole, a known antiulcer drug with IC50 19.3 μg/mL. The antiulcer potency of PGP was evaluated in ethanol stress induced gastric ulcer model in vivo. About 84% reduction in ulcer index; enhanced mucosal recovery, normalization of H(+), K(+)-ATPase, antioxidant and antioxidant enzymes substantiated the antiulcer potentials of PGP. Mucosal recovery could be attributed to cytoprotective and DNA protective ability of PGP that can help in mucosal layer regeneration. Further, PGP was also effective in inhibiting Helicobacter pylori as per growth inhibition assay followed by scanning electron microscopic studies suggesting that PGP is effective in curbing the growth of H. pylori, which is responsible for ∼70% of gastric ulcer/cancer incidences.