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Despite being an essential element for normal functioning of cells and organisms, iron, in excess, can induce oxidative stress by generating reactive oxygen species. A water-soluble, non-toxic iron chelator can reduce the iron-induced oxidative stress in the body as well as help in extricating excess iron. Herein, we report an Ocimum sanctum -derived antioxidant polysaccharide (OSP) that inhibits the deleterious effect of iron. Ocimum sanctum is a widely acknowledged medicinal plant contributing toward several biological benefits. Besides showing good hydroxyl radical scavenging activity, OSP could bind to ferric and ferrous ions to prevent their participation in redox reactions as revealed from modified 2-deoxyribose assays, carried out under various conditions. It also acted as an iron modulator to prevent site-specific damage and was effective in protecting mouse fibroblast L929 cells against iron induced death.

Quorum-sensing (QS) is known to play an essential role in regulation of virulence factors and toxins during Pseudomonas aeruginosa infection which may frequently cause antibiotic resistance and hostile outcomes of inflammatory injury. Therefore, it is an urgent need to search for a novel agent with low risk of resistance development that can target QS and inflammatory damage prevention as well. Andrographis paniculata, a herbaceous plant under the family Acanthaceae, native to Asian countries and also cultivated in Scandinavia and some parts of Europe, has a strong traditional usage with its known antibacterial, anti-inflammatory, antipyretic, antiviral and antioxidant properties. In this study, three different solvent extracts (viz., chloroform, methanol and aqueous) of A. paniculata were examined for their anti-QS and anti-inflammatory activities. Study was carried out to assess the effect on some selected QS-regulatory genes at transcriptional level using Real Time-PCR. In addition, ability to attenuate MAPK pathways upon P. aeruginosa infection was performed to check its potential anti-inflammatory activity. Chloroform and methanol extracts showed significant reduction (p < 0.05) of the QS-controlled extracellular virulence factors in P. aeruginosa including the expression of pyocyanin, elastase, total protease, rhamnolipid and hemolysin without affecting bacterial viability. They also significantly (p < 0.05) reduced swarming motility and biofilm formation of P. aeruginosa. The chloroform extract, which was found to be more effective, decreased expression of lasI, lasR, rhlI and rhlR by 61%, 75%, 41%, and 44%, respectively. Moreover, chloroform extract decreased activation of p-p38 and p-ERK1/2 expression levels in MAPK signal pathways in P. aeruginosa infected macrophage cells. As the present study demonstrates that A. paniculata extracts inhibit QS in P. aeruginosa and exhibit anti-inflammatory activities, therefore it represents itself as a prospective therapeutic agent against P. aeruginosa infection., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Increasing bacterial resistance to common drugs is a major public health concern for the treatment of infectious diseases. Certain naturally occurring compounds of plant sources have long been reported to possess potential antimicrobial activity. This study was aimed to investigate the antibacterial activity and possible mechanism of action of andrographolide (Andro), a diterpenoid lactone from a traditional medicinal herb Andrographis paniculata. Extent of antibacterial action was assessed by minimal bactericidal concentration method. Radiolabeled N-acetyl glucosamine, leucine, thymidine, and uridine were used to determine the effect of Andro on the biosyntheses of cell wall, protein, DNA, and RNA, respectively. In addition, anti-biofilm potential of this compound was also tested. Andro showed potential antibacterial activity against most of the tested Gram-positive bacteria. Among those, Staphylococcus aureus was found to be most sensitive with a minimal inhibitory concentration value of 100 μg/mL. It was found to be bacteriostatic. Specific inhibition of intracellular DNA biosynthesis was observed in a dose-dependent manner in S. aureus. Andro mediated inhibition of biofilm formation by S. aureus was also found. Considering its antimicrobial potency, Andro might be accounted as a promising lead for new antibacterial drug development.

Allylpyrocatechol (APC) is responsible for the antiinflammatory activity exhibited by the methanolic extract of leaves of Piper betle. As antiinflammatory compounds may display antioxidant properties and vice versa, we investigated the antioxidant effect of APC. APC effectively reduced phorbol-myristate-acetate-induced generation of reactive oxygen species and superoxide in murine peritoneal macrophages as well as inhibited Escherichia-coli-induced phagocytic activity of macrophages. Furthermore, pBluescript SK(+) plasmid DNA damage induced by addition of sodium ascorbate was attenuated by APC as it inhibited transformation of the supercoiled form to a relaxed form. In addition, APC increased the enzymatic (catalase) and nonenzymatic (GSH) antioxidant components of murine macrophages. Taken together, APC exhibited an antioxidant activity which was mediated both via decreased generation of free radicals along with increase in cellular antioxidants., (Copyright © 2012 John Wiley & Sons, Ltd.)

The healing activity of black tea (BT) and BT fermented with Candida parapsilosis and kombucha culture, designated as CT and KT respectively against the indomethacin-induced stomach ulceration has been studied in a mouse model. The KT sample (KT4) produced by fermenting BT for four days, showed the best DPPH radical scavenging capacity and phenolics contents. Hence the ulcer-healing activity of KT4 was compared with those of CT4 and BT. All the tea extracts (15 mg kg(-1)) could effectively heal the gastric ulceration as revealed from the histopathological and biochemical studies, with relative efficacy as KT4 > CT4 ∼ BT. The healing capacities of the tea extracts could be attributed to their antioxidant activity as well as the ability to protect the mucin content of the gastric tissues. In addition, the ability of KT4 to reduce gastric acid secretion might also contribute to its ulcer-healing activity. The tea preparation KT4 (15 mg kg(-1)) was as effective as the positive control, omeprazole (3 mg kg(-1)) in ulcer healing.

Earlier we had shown that on the 3 (rd) day of its administration to mice, indomethacin (18 mg kg (-1), P. O.) produced maximum stomach ulceration with a damage score of 3.46, which was reduced by a 3-day treatment with the methanol extract of Myristica malabarica (40 mg kg (-1), P. O.) and omeprazole (3 mg kg (-1), P. O.) to 0.95 and 0.82, respectively. Presently, we investigated the possible role of the test samples in modulating PG synthesis and angiogenesis for their healing action. The ulceration was found to be associated with suppression of PGE (2), VEGF and vWF VIII, and an increase in EGF and endostatin levels. Treatment with the plant extract reversed all these parameters accounting for its healing activity. However, despite providing similar healing, omeprazole did not alter these parameters.

Indomethacin caused maximum stomach ulceration in mice on the 3rd day, which was associated with reduction of plasma total antioxidant status (TAS), COX-1, COX-2, mucosal PGE(2), VEGF, and vWF, along with an increase in endostatin levels. Treatment with the phytochemical allylpyrocatechol (5 mg/kg, p.o. for 3 days) provided significant ulcer healing by reversing these biochemical parameters, as well as increasing the EGF expression more than that observed due to ulceration. Omeprazole (3 mg/kg, p.o. for 3 days) provided a similar healing by improving TAS and mucin levels, without significantly altering the other parameters.

Background: The present study was undertaken to evaluate the potential of the rhizomes of the Indian medicinal plant, Picrorhiza kurroa in healing indomethacin-induced acute stomach ulceration in mice and examine its capacity to modulate oxidative stress and the levels of prostaglandin (PGE2) and EGF during the process., Methods: Male swiss albino mice, ulcerated with indomethacin (18 mg/kg, p. o., single dose) were treated up to 7 days with different doses of the methanol extract of P. kurroa rhizomes (designated as PK). The healing capacity of the most effective dose of PK (20 mg/kg, p. o. x 3 d) was compared with that of omeprazole (Omez) (3 mg/kg, p. o. x 3 d). The effects of the drug-treatment for one and three days on the biochemical parameters were assessed by comparing the results with that of untreated mice of the 1st and 3rd day of ulceration. The stomach tissues of the mice were used for the biochemical analysis., Results: The macroscopic indices revealed maximum ulceration on the 3rd day after indomethacin administration, which was effectively healed by PK. Under the optimized treatment regime, PK and Omez reduced the ulcer indices by 45.1% (P < 0.01), and 76.3% respectively (P < 0.001), compared to the untreated ulcerated mice. Compared to the ulcerated untreated mice, those treated with PK for 3 days showed decreased the levels of thiobarbituric acid reactive substances (TBARS) (32.7%, P < 0.05) and protein carbonyl (37.7%, P < 0.001), and increased mucin (42.2%, P < 0.01), mucosal PGE2 (21.4%, P < 0.05), and expressions of COX-1 and 2 (26.9% and 18.5%, P < 0.05), EGF (149.0%, P < 0.001) and VEGF (56.9%, P < 0.01). Omez reduced the TBARS (29.4%, P < 0.05), and protein carbonyl (38.9%, P < 0.001), and increased mucin (38.3%, P < 0.01), without altering the other parameters significantly., Conclusion: PK (20 mg/kg, p. o. x 3 days) could effectively heal indomethacin-induced stomach ulceration in mice by reducing oxidative stress, and promoting mucin secretion, prostaglandin synthesis and augmenting expressions of cyclooxygenase enzymes and growth factors.

The healing activity of the methanol extract of the spice rampatri, Myristica malabarica, (RM) and omeprazole against indometacin-induced stomach ulceration has been studied in a mouse model. Treatment with RM (40 mg kg(-1) per day) and omeprazole (3 mg kg(-1) per day) for 3 days could effectively heal the stomach ulceration, as revealed from the ulcer indices and histopathological studies. Compared with the ulcerated group, treatment with RM and omeprazole for 3 days reduced the macroscopic damage score by approximately 72% and 76%, respectively (P<0.001), establishing the efficacy of RM. The extent of ulcer healing offered by 3 days' treatment with RM or omeprazole was better than that observed with natural recovery over 5 and 7 days (P<0.05). The healing capacities of RM and omeprazole could be attributed to their antioxidant activity as well as the ability to enhance the mucin content of the gastric tissues. Both drugs reduced lipid peroxidation (by 42-44%) and protein carbonyl content (by 34%), and augmented non-protein thiol levels beyond normal values. Furthermore, RM improved the mucin level beyond the normal value, while omeprazole restored it to near normalcy.

A major problem in the management of visceral leishmaniasis, especially in the Indian subcontinent, is the growing unresponsiveness to conventional antimonial therapy, indicating the urgent need to identify new antileishmanial compounds. This study was undertaken to evaluate the antileishmanial activity of the fruit rind of Myristica malabarica that is used as a spice and is also credited with medicinal properties. The antipromastigote activity of different extracts/fractions of M. malabarica and its constituent diarylnonanoids were evaluated in Leishmania donovani promastigotes (MHOM/IN/83/AG83) using the MTS-PMS assay. Preliminary screening of the ether extract (R1) with its crude methanol fraction (R2) and two fractions (R3 and R4) revealed that R2 had potent leishmanicidal activity (IC(50) 31.0 microg/mL), whereas R3 and R4 showed poor activity. Fractionation of R2 yielded four diarylnonanoids (malabaricones A-D, designated as Mal A, Mal B, Mal C and Mal D, respectively). The IC(50) values of Mal A-D were 16, 22, 27 and >50 microg/mL, respectively. Taken together, the data suggest that the methanol extract of M. malabarica, especially its constituent compounds, Mal A and Mal B, have promising antileishmanial activity meriting further investigations regarding the underlying molecular mechanism(s) of action with a view towards future drug development., ((c) 2007 John Wiley & Sons, Ltd.)

The leaves of Piper betle (locally known as Paan) have long been in use in the Indian indigenous system of medicine for the relief of pain; however, the underlying molecular mechanisms of this effect have not been elucidated. The anti-inflammatory and immunomodulatory effects of an ethanolic extract of the leaves of P. betle (100 mg kg(-1); PB) were demonstrated in a complete Freund's adjuvant-induced model of arthritis in rats with dexamethasone (0.1 mg kg(-1)) as the positive control. At non-toxic concentrations of PB (5-25 microg mL(-1)), a dose-dependent decrease in extracellular production of nitric oxide in murine peritoneal macrophages was measured by the Griess assay and corroborated by flow cytometry using the nitric oxide specific probe, 4,5-diaminofluorescein-2 diacetate. This decreased generation of reactive nitrogen species was mediated by PB progressively down-regulating transcription of inducible nitric oxide synthase in macrophages, and concomitantly causing a dose-dependent decrease in the expression of interleukin-12 p40, indicating the ability of PB to down-regulate T-helper 1 pro-inflammatory responses. Taken together, the anti-inflammatory and anti-arthrotic activity of PB is attributable to its ability to down-regulate the generation of reactive nitrogen species, thus meriting further pharmacological investigation.

The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay of the ethanol extracts of three varieties (Bangla, sweet, and Mysore) of Piper betel (pan) revealed the Bangla variety to possess the best antioxidant activity that can be correlated with the total phenolic content and reducing powers of the respective extracts. Column chromatography of the extract of the Bangla variety led to the isolation of chevibetol (CHV), allylpyrocatechol (APC), and their respective glucosides. The HPTLC analyses of the extracts revealed similar chemical profiles in all three P. betel varieties, although the concentrations of CHV and APC were significantly less in the sweet and Mysore varieties. Among the isolated compounds, APC showed the best results in all the in vitro experiments. It could prevent Fe(II)-induced lipid peroxidation (LPO) of liposomes and rat brain homogenates as well as gamma-ray-induced damage of pBR322 plasmid DNA more efficiently than CHV. The superior anti-LPO and radioprotective activities of APC vis-à-vis those of CHV could not be explained by their respective Fe(II) chelation and .OH radical scavenging capacities. The better ability of APC to scavenge O2-. radicals and H2O2 might account for the results.

The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay of the ether, methanol, and aqueous extracts of the spice Myristica malabarica (rampatri) revealed the methanol extract to possess the best antioxidant activity. Column chromatography of the methanol extract led to the isolation of a new 2-acylresorcinol and four known diarylnonanoids of which the diarylnonanoid, malabaricone C, showed the maximum DPPH scavenging activity. Malabaricone C could prevent both Fe(II)- and 2,2'-azobis(2-amidinopropane)dihydrochloride-induced lipid peroxidation (LPO) of rat liver mitochondria more efficiently than curcumin. The anti-LPO activity of malabaricone C was attributed to its better radical scavenging and Fe(II) chelation capacities. The superior activity of malabaricone C was rationalized by a systematic structure-activity correlation of the results obtained with the structurally related diarylnonanoids and curcumin. Malabaricone C also prevented the gamma-ray-induced damage of pBR322 plasmid DNA in a concentration-dependent manner. The radioprotective activity was found to correlate with its (*)OH radical scavenging property, which matched well with that of d-mannitol.

The radioprotective activity of Piper betel ethanolic extract (PE) has been studied using rat liver mitochondria and pBR 322 plasmid DNA as two model in vitro systems. The extract effectively prevented gamma-ray induced lipid peroxidation as assessed by measuring thiobarbituric acid reactive substrates, lipid hydroperoxide and conjugated diene. Likewise, it prevented radiation-induced DNA strand breaks in a concentration dependent manner. The radioprotective activity of PE could be attributed to its hydroxyl and superoxide radicals scavenging property along with its lymphoproliferative activity. The radical scavenging capacity of PE was primarily due to its constituent phenolics, which were isolated and identified as chevibetol and allyl pyrocatechol.

Abstract: The protective activities of Emblica officinalis, Terminalia bellerica and Terminalia chebula ethanol extracts against photosensitization-induced oxidation of rat liver mitochondrial lipid were assessed. All the extracts could effectively prevent lipid peroxidation, as assessed by measuring thiobarbituric acid-reactive substrates, lipid hydroperoxide, conjugated diene and 4-hydroxynonenal. The E. officinalis extract was the most potent, revealing its superior ability to scavenge 1O2. The extracts also afforded excellent protection against iron-mediated lipid peroxidation that might also be useful in reducing photo-induced iron toxicity. The activities of the extracts were primarily due to their constituent phenolics. [Copyright &y& Elsevier]