Effect of dehydrozingerone, a half analog of curcumin on dexamethasone-delayed wound healing in albino rats.

Oxidative stress is triggered by the wound which results in the production of reactive oxygen species (ROS), thereby delaying normal wound repair. Therefore, it is important to reduce the level of ROS to improve healing. A known antioxidant, dehydrozingerone (DHZ) was synthesized and selected for the study. The authors aimed to investigate the wound healing action of topical (100 mg/wound) and systemic (100 mg/kg, p. o.). DHZ on different wound models in normal and dexamethasone (DEX)-suppressed healing. Topical DHZ showed a significant (P < 0.05) rise in tensile strength when compared to control in normal healing. Significant (P < 0.05) wound closure was observed from 3 to 9 days in DHZ oral and gel treated groups. There was a significant (P < 0.05) rise in hydroxyproline content with the DHZ treated groups when compared to control. Systemic DHZ exhibited a significant (P < 0.05) increase in lysyl oxidase (LO) levels of 3.73 ± 0.15 nmol of H(2)O(2) when compared to control. In DEX-suppressed healing, showed good pro-healing activity with respect to the parameters mentioned above. DHZ treatment exhibited a parabolic dose response of ROS inhibition with a plateau effect at 75 µM. There was a steady and constant increase in the % NO inhibition with increasing doses of DHZ. Oral DHZ is effective in accelerating the healing process in both normal and dexamethasone-suppressed wounds. Our study suggests that DHZ (half analog of curcumin) supplementation reduces the steroid-induced delay in wound healing.

Pro-healing effects of morin, a natural antioxidant, on normal and dexamethasone-impaired wounds.

BACKGROUND: The aim of the study was to investigate the effects of morin on skin breaking strength, hydroxyproline, lysyl oxidase, DNA and RNA content of experimentally inflicted wounds in rats. METHODS: This study was performed on albino rats of either sex at the Central Animal Research Facility (CARF), Manipal University. RESULTS: Morin showed significant wound contraction on day 7 as compared to control with mean closure of 47.44±6.07% in excision wound model. Granulation tissue breaking strength was significantly increased (p<0.05) in the morin treated group with 180.2±7.94 g when compared to control at 151.2±6.99 g. There was a significant increase in hydroxyproline content with the morin treated group when compared to control with 3.41±0.33 µg/mg of granulation tissue. Similarly, the wound parameters were improved with the morin treated group in dexamethasone delayed healing. CONCLUSIONS: Our results suggest that morin treatment accelerates the healing process delayed by concurrent use of steroids.

Sesamol prevents doxorubicin-induced oxidative damage and toxicity on H9c2 cardiomyoblasts.

OBJECTIVES: Exposure to toxicants like doxorubicin (Dox) damages cellular components by generating reactive oxygen species (ROS). This can be attenuated using free radical scavengers and/or antioxidants. METHODS: Dox-exposed cardiac myoblasts (H9c2 cells) were treated with sesamol (12.5, 25 and 50 µm), a natural phenolic compound. Intracellular ROS inhibition, cell viability and analysis of antioxidant and biochemical markers such as superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, reduced/oxidized glutathione, lipid peroxidation and protein carbonyl content were performed. The effect of sesamol treatment on the cytotoxic and genotoxic parameters was studied by monitoring the signalling proteins involved in the apoptotic pathway. KEY FINDINGS: Dox triggered cellular and genetic damage by increasing levels of intracellular ROS, thereby decreasing cell viability and increasing apoptosis. Sesamol reversed the cytotoxic and genotoxic effects of Dox. In addition, sesamol attenuated the pro-apoptotic proteins and improved the anti-apoptotic status. Sesamol pre-treatment also alleviated the disturbed antioxidant milieu by preventing ROS production and improving endogenous enzyme levels. CONCLUSIONS: Among the different doses tested, 50 µm of sesamol showed maximum protection against Dox-induced oxidative damage. This reflects the significance of sesamol in ameliorating the deleterious effects associated with cancer chemotherapy.

Evaluation of in vitro antioxidant and in vivo analgesic potential of Terminalia paniculata aqueous bark extract.

The Terminalia genus includes plants that are used in a variety of food, nutritional products, and traditional medicines. Aqueous bark extract of Terminalia paniculata (TPW) was screened for its antioxidant and analgesic potential. The major polyphenols were identified by high-performance liquid chromatography. In vitro antioxidant potential of TPW was investigated by 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(2-)) radical assay, nitric oxide (NO) scavenging, superoxide scavenging (O(2-)), Fe(2+) chelating (O-phenanthroline), and ferric reducing/antioxidant power (FRAP) assay. We evaluated the effects of TPW on cell viability, lipopolysaccharide (LPS)-stimulated reactive oxygen species (ROS), nitrite, and cytokines (interleukin [IL] 6 and tumor necrosis factor alpha [TNF-α]) in RAW 264.7 murine macrophages. Evaluation of analgesic activity of TPW was performed using acetic acid-induced writhing and hot plate test in mice. Phytochemical analysis showed the presence of four polyphenols, namely, gallic acid, ellagic acid, rutin, and quercetin. TPW showed maximum superoxide, ABTS(2-), NO, DPPH inhibition, and Fe(2+-)chelating property at 400 µg/mL, respectively. FRAP value was 4.5±0.25 µg Fe(II)/g. TPW, per se, did not affect RAW 264.7 cell viability. In LPS-induced RAW 264.7 cells, TPW attenuated the elevation in ROS, nitrite, IL-6, and TNF-α levels. TPW (100-400 mg/kg, orally) significantly reduced the number of writhes in a dose-dependent manner compared with the control. Similarly, TPW (400 mg/kg, orally) evoked a significant increase in the maximum percentage effect in the hot plate test. The study suggests the efficacy of aqueous bark extract of T. paniculata as a potential antioxidant and analgesic agent.

Antidiabetic, antihyperlipidemic and antioxidant effects of the flavonoid rich fraction of Pilea microphylla (L.) in high fat diet/streptozotocin-induced diabetes in mice.

The present study describes the antidiabetic effect of the flavonoid rich fraction of Pilea microphylla (PM1). HPLC characterization of PM1 revealed the presence of polyphenols viz., chlorogenic acid, rutin, luteolin-7-O-glucoside, isorhoifolin, apigenin-7-O-glucoside, and quercetin. PM1 inhibited dipeptidyl peptidase IV (DPP-IV) in vitro with an IC(50) of 520.4±15.4 µg/ml. PM1, at doses of 300, 600 and 900 mg/kg i.p., also produced dose-dependent mean percent reductions of 9.9, 30.6 and 41.0 in glucose excursion (AUC(0-120 min)) respectively in lean mice. However, even the highest dose of PM1 did not alter normoglycemic condition. PM1 at dose of 100 mg/kg/day, i.p. for 28 days produced significant (p<0.05) reduction in body weight, plasma glucose (PG), triglycerides (TG) and total cholesterol (TC) content in high-fat streptozotocin-induced diabetic mice. PM1 also improved oral glucose tolerance significantly (p<0.05) with mean percentage reduction of 48.0% in glucose excursion (AUC(0-120 min)) and significantly (p<0.05) enhanced the endogenous antioxidant status in mice liver compared to diabetic control. PM1 preserved islet architecture and prevented hypertrophy of hepatocytes as evident from the histopathology of pancreas and liver. PM1 did not show any detectable hematological toxicity at therapeutic doses. In conclusion, PM1 exhibits antidiabetic effect possibly by inhibiting DPP-IV and improving antioxidant levels in high fat diet/streptozotocin (HFD/STZ) diabetic mice.

Polyphenolic fraction of Pilea microphylla (L.) protects Chinese hamster lung fibroblasts against γ-radiation-induced cytotoxicity and genotoxicity.

Present study was designed to compare cytoprotective and antigenotoxic activity of the polyphenolic fraction of Pilea microphylla (PM1) with that of its active polyphenolic constituents against γ-radiation in V79 cells. PM1 was standardized with respect to the polyphenols present by RP-HPLC. It was evaluated for its free radical scavenging potential using Fenton reaction-induced DNA damage and lipid peroxidation. Further, PM1 was subjected against γ-radiation-induced cytotoxicity and genotoxicity in V79 cells. PM1 significantly reduced free radical-mediated calf thymus DNA damage and lipid peroxidation. Among the concentrations tested (12.5, 25 and 50 µg/ml) for radioprotection, PM1 at 25 µg/ml exhibited maximum protection. Further, when compared with constituent polyphenols viz., rutin, quercetin and chlorogenic acid (concentrations equivalent to that present in PM1-25 µg/ml), a combination of polyphenols was found most effective in preventing γ-radiation-induced cytotoxicity and genotoxicity. To conclude, radioprotection is possibly a synergistic effect of the phytochemicals present in the herbal extract, rather than any single component.

Normal and delayed wound healing is improved by sesamol, an active constituent of Sesamum indicum (L.) in albino rats.

UNLABELLED: ETHNO-PHARMACOLOGICAL RELEVANCE: The seeds of Sesamum indicum Linn. (Pedaliaceae) has been used traditionally for the treatment of wounds in Buldhana district of Maharashtra state. Sesamol is the main anti-oxidative constituent contained mainly in the processed sesame seed oil which has not been explored scientifically for its wound healing activity. AIM OF THE STUDY: To investigate the influence of sesamol (SM) on wound repair, both in normal and dexamethasone (DM) delayed healing processes in albino rats. MATERIALS AND METHODS: Incision, excision and dead space wounds were inflicted on albino rats (180-220 g) of either sex, under ketamine anaesthesia. Group I served as control, group II received SM 50 mg/kg i.p., group III was treated with dexamethasone (DM) i.m. (0.17 mg/kg) and SM+DM was given to group IV. The tensile strength, wound contraction, hydroxyproline, lysyl oxidase and total RNA and DNA levels (in granulation tissue) were measured. RESULTS: The tensile strength significantly (p<0.05) increased with SM at 471.40±14.66 g when compared to control at 300.60±9.16 g in normal and DM suppressed healing. No significant change was observed in duration of wound contraction and lysyl oxidase when compared to control at 2.98±0.10 mg. SM treated rats showed a significant (p<0.05) rise in hydroxyproline levels at 6.45±0.45 mg when compared to control at 1.75±0.20 mg. CONCLUSION: These results indicate that sesamol could be a promising drug in normal as well as delayed wound healing processes.

Vasorelaxant and antihypertensive effect of Cocos nucifera Linn. endocarp on isolated rat thoracic aorta and DOCA salt-induced hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Cocos nucifera Linn. (Arecaceae) have long been used in traditional medicine for the treatment of cardio-metabolic disorders. AIM OF THE STUDY: To evaluate the ethanolic extract of Cocos nucifera Linn. endocarp (CNE) for its vasorelaxant activity on isolated rat aortic rings and antihypertensive effects in deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats. MATERIALS AND METHODS: Cocos nucifera Linn. endocarp was extracted with ethanol and characterized by HPLC. CNE was examined for its in vitro vascular relaxant effects in isolated norepinephrine, phenylephrine or potassium chloride pre-contracted aortic rings (both intact endothelium and denuded). In vivo anti-hypertensive studies were conducted in DOCA salt-induced uninephrectomized male Wistar rats. RESULTS: Removal of endothelium or pretreatment of aortic rings (intact endothelium) with l-NNA (10µM) or ODQ (10 µM) followed by addition of contractile agonists prior to CNE significantly blocked the CNE-induced relaxation. Indomethacin (10µM) and atropine (1 µM) partially blocked the relaxation, whereas glibenclamide (10 µM) did not alter it. CNE significantly reduced the mean systolic blood pressure in DOCA salt-induced hypertensive rats (from 185.3 ± 4.7 mmHg to 145.6±6.1 mmHg). The activities observed were supported by the polyphenols, viz. chlorogenic acid, vanillic acid and ferulic acid identified in the extract. CONCLUSIONS: These findings reveal that the vasorelaxant and antihypertensive effects of CNE, through nitric oxide production in a concentration and endothelium-dependent manner, is due to direct activation of nitric oxide/guanylate cyclase pathway, stimulation of muscarinic receptors and/or via cyclooxygenase pathway.