Bronco T (Shirisadi kasaya), a polyherbal formulation prevents LPS induced septicemia in rats.

OBJECTIVE: Here, Bronco T (BT), a polyherbal formulation developed in 1984 for treating asthma, has been repurposed against septicemia-induced ALI. MATERIALS AND METHODS: Lipopolysaccharides (3 mg/kg BW) were injected intraperitoneally before 24 hours of surgery to assess the cardiorespiratory parameters, blood PaO2/FiO2 and MPO, pulmonary water content and histological changes in the lungs. The pentoxifylline (PTX) (25 mg/kg BW) was used as the positive control and given one hour before LPS. BT was given 3 hours (orally at different doses of 3, 1.5 and 0.75 g/kg BW) before LPS. RESULTS: The LPS treated group showed significant bradypnea, hypotension and bradycardia, through elongated peaks (RR) and (MAP) respectively and finally death after 95 minutes of LPS injection. The PTX and BT (3 g/kg BW) pretreatment significantly prevented these changes (dose-dependent in the BT group). The survival in these groups was maintained up to 190 min after LPS. The Pentoxifylline showed a better response (75%) than Bronco T (72%). In both the treatments, a significant decrease in pulmonary water content and minimal neutrophil infiltration and intact alveoli-capillary membrane was seen in the transverse section (T.S) of the lungs. CONCLUSIONS: Significant improvement was noted in survival time with lesser tissue damage and improved pulmonary function was observed by pre-treating with Bronco T in LPS induced septicemia.

Impact of Nano Preparation of Phytoconstituents in Medulloblastoma.

The conventional cancer treatment strategies from chemotherapy to surgery often lead to inadequate results which in some cases lead to relapsing of the tumor being treated. Medulloblastoma witness 30% relapse rate which is universally fatal among children. Although the treatment of primary medulloblastoma is well established including surgical excision, postsurgical irradiation, and, more recently, chemotherapy, there is no established treatment for its recurrence. Despite efforts to improve its therapy, frequent long-haul survivors have been recorded in the world's medical literature. In this book chapter, we have attempted to focus light on the nano preparation of phytoconstituents as an alternative approach as it has advantage of providing better bioavailability of the compound in terms of crossing the blood-brain barrier and an additional benefit in terms of limited adverse effects of the natural product over the traditional chemotherapeutic approaches. In recent times, biological methods or green approaches in the case of plants have received immense attention due to its safety and lack of contamination in the process. In this chapter, we will explore some plant products that have been incorporated into nanocarriers to improve their bioavailability in this tumor treatment.

Role of Ayurvedic Plants as Anticancer Agents.

The use of natural products has been increasing at a rapid pace, worldwide, with the aim to maintain a healthy lifestyle and to modify one's dietary habits. Ayurveda is a domain that has numerous wealth of information concerning medicinal plants and its part in controlling numerous ailments, such as neoplastic, cardiovascular, neurological plus immunological ailments. The use of such medicinal plants is important for preventing such diseases, especially "cancer" which is the succeeding foremost cause of mortality collectively. Even though abundant developments have been made in the management and control of cancer progression, substantial deficits and scope for advancement still continue to be unchanged. Several lethal adjacent consequences occur throughout the course of chemotherapy. Natural treatments, such as the use of plant-derived products in the treatment of cancer, might reduce the hostile side effects. Presently, a few plant-based products and its phytoconstituents are being utilized for the management of cancer. Here we have focused on numerous plant-derived phytochemicals and promising compounds from these plants to act as anticancer agents, along with their mechanisms of action.

Evaluation of Chenopodium ambrosioides oil as a potential source of antifungal, antiaflatoxigenic and antioxidant activity.

Essential oil extracted from the leaves of Chenopodium ambrosioides Linn. (Chenopodiaceae) was tested against the aflatoxigenic strain of test fungus Aspergillus flavus Link. The oil completely inhibited the mycelial growth at 100 microg/ml. The oil exhibited broad fungitoxic spectrum against Aspergillus niger, Aspergillus fumigatus, Botryodiplodia theobromae, Fusarium oxysporum, Sclerotium rolfsii, Macrophomina phaseolina, Cladosporium cladosporioides, Helminthosporium oryzae and Pythium debaryanum at 100 microg/ml. The oil showed significant efficacy in inhibiting the aflatoxin B1 production by the aflatoxigenic strain of A. flavus. During in vivo investigation it protected stored wheat from different storage fungi for one year. Chenopodium oil also exhibited potent antioxidant activity when tested by ABTS method. All these observations suggest the possible exploitation of the Chenopodium oil as potential botanical fungitoxicant in ecofriendly control of post harvest biodeterioration of food commodities from storage fungi.

Interaction of Strychnos nux-vomica-products and iron: with reference to lipid peroxidation.

In this paper, it has been investigated that strychnine, the major active principle in the alcoholic extract of the seeds of Strychnos nux-vomica, is responsible for its antilipid peroxidative property. The mechanism of action of this drug is through the chelation of the free iron in the system. It has also been observed that strychnine does not have any pro-oxidant-property, because it does not convert Fe3+ to Fe2+ and vice versa in the reaction system, as has been observed with several other antioxidants.

The interaction of Rubia cordifolia with iron redox status: a mechanistic aspect in free radical reactions.

The present publication investigates the antioxidant property and mechanistic aspect of alcoholic extract of R. cordifolia. The extract of R. cordifolia has shown significant inhibitory effect on FeSO4 induced lipid peroxidation. Study with iron redox status showed that R. cordifolia extract reduced or oxidixed; Fe3+ or Fe2+ respectively, in a dose dependent manner. Results with superoxide anion (O2-.) and hydroxyl radical (OH.), showed no radical scavenging activity. The alcoholic extract significantly maintains the reduced glutathione content both in time and dose dependent manner. It also reduced the rate of depletion of reduced glutathione (GSH) level in presence of ferrous sulphate (FeSO4) and cumene hydroperoxide (CHP). On the basis of these observations, it can be concluded that the antioxidant property of R. cordifolia is due to a direct interaction with iron.

Effect of Semicarpus anacardium on the cell cycle of DU-145 cells.

The nuts of Semicarpus anacardium (Anacardiaceae) are one of the most favoured medicine in the Indian System of Medicine for the management of arthritis and several other free radical mediated diseases. It is also recommended for the management of the breast cancer. In this report we have investigated its role on the cell cycle and cell viability on the DU-145 cells (transformed prostate cells) by flow cytometric technique. It was observed that the plant extract significantly arrests the cell cycle at G-1 stage, and induced apoptosis. On higher concentrations, it affects the cell viability. The response was dose dependent.

Rubiadin, a new antioxidant from Rubia cordifolia.

Rubiadin, a dihydroxy anthraquinone, isolated from alcoholic extract of Rubia cordifolia, possesses potent antioxidant property. It prevents lipid peroxidation induced by FeSO4 and t-butylhydroperoxide (t-BHP) in a dose dependent manner. The per cent inhibition was more in the case of Fe2+ induced lipid peroxidation. The antioxidant property of the preparation has been found to be better than that of EDTA, Tris, mannitol, Vitamin E and p-benzoquinone.

Bacopa monniera Linn. as an antioxidant: mechanism of action.

Bacopa monniera, Linn. (Brahmi: Scrophulariaceae) an Ayurvedic medicine is clinically used for memory enhancing, epilepsy, insomnia and as mild sedative. For the first time the effect of alcohol and hexane fraction of Brahmi has been studied on FeSO4 and cumene hydroperoxide induced lipid peroxidation. Alcohol fraction showed greater protection with both inducers. Results were compared with known antioxidants tris, EDTA and a natural-antioxidant vitamin E. The effect of Brahmi was also examined on hepatic glutathione content. The mechanism of action could be through metal chelation at the initiation level and also as chain breaker. The results suggested that Brahmi is a potent antioxidant. The response of Brahmi was dose dependent. Tris, an hydroxyl trapper did not show any protection in comparison to Brahmi where as EDTA and vitamin E did protect against FeSO4. In experimental conditions 100 micrograms Brahmi extract (alcoholic) was equivalent to 247 micrograms of EDTA (0.66 microM) and 58 micrograms of vitamin E. Interestingly Brahmi only slightly protected the autooxidation and FeSO4 induced oxidation of reduced glutathione on lower doses 100 micrograms/ml and below, but on higher concentrations it enhanced the rate of oxidation.

Studies on the inhibitory effect of Strychnos nux vomica-alcohol extract on iron induced lipid peroxidation.

This report investigates the antioxidant property of Strychnos nux vomica Linn, alcohol extract on FeS04-induced lipid peroxidation in vitro. The results have been compared to those of vitamin E, parabenzoquinone, Tris, mannitol and EDTA. Tris and mannitol, the standard hydroxyl trappers failed to block this process. Interestingly EDTA, a strong metal chelator, significantly blocks the process of lipid peroxidation. S. nux vomica inhibits the lipid peroxidation in the dose dependent manner. The inhibition of lipid peroxidation was reversed by adding high concentration of Fe(2+). This suggests the mechanism of action of S. nux vomica through the chelation of Fe(++)/Fe(+++) ion in the system and not by trapping the hydroxyl radicals. This extract significantly maintains the hepatic glutathione content also in the time and dose dependent manner even in the presence of FeSO(4), which is not the case with EDTA. It also inhibits the process of lipid peroxidation once induced.

Antioxidant and anti-inflammatory property of Sandhika: a compound herbal drug.

The present study was envisaged to assess the rationality for the use of "Sandhika", a popular Ayurvedic drug in rheumatoid arthritis. This drug, when tested against carrageenan induced paw oedema and cotton pellet granuloma, showed significant anti-inflammatory activity at the dose of 0.25 g/kg body weight. The antioxidant property was assessed by determining cumene hydroperoxide (CHP) induced lipid peroxidation and reduced glutathione content in rat liver homogenate (in vitro). Experiments show the significant protection against lipid peroxidation at the dose of 80 micrograms/ml, measured as reduction in the level of malondialdehyde (MDA) induced by 1.5 mM cumene hydroperoxide (CHP). This effect was accompanied by the maintained reduced glutathione (GSH) content in drug treated rats. Oral treatment of drug up to 2 g/kg body weight for 15 days did not show any rise in serum transaminases (SGOT and SGPT). The results suggest that "Sandhika" which is an indigenous drug for inflammation with no detectable adverse effect, might be acting through scavenging the free radicals.

Hepatoprotective and toxicological evaluation of hepatomed, an ayurvedic drug.

Hepatoprotective effect of Hepatomed (an ayurvedic drug containing water extract of 6 medicinal plants) has been studied on cumene hydroperoxide (CHP) induced lipid peroxidation and reduced glutathione content in rat liver homogenate. In vitro experiments show significant reduction in the level of malondialdehyde (MDA) induced by 1.5 mM cumene hydroperoxide(CHP). Glutathione content was almost maintained to normal in drug treated rats. Oral treatment of drug up to 3 ml/100 g body weight for 15 days did not show any rise in serum GOT and GPT. On similar doses, significant choleratic effect was observed without any adverse histological changes after 4 days treatment. The results suggest that 'Hepatomed' is a strong hepatoprotective ayurvedic medicine with no detectable adverse effects.

Protective effect of Rubia cordifolia on lipid peroxide formation in isolated rat liver homogenate.

Rubia cordifolia Linn. (Rubiaceae) is an important component of the ayurvedic system of medicine. It has a variety of uses such as blood purifier, immunomodulant, antiinflammatory and anti-PAF. In this report the anti-peroxidative property of the solvent free alcoholic extract of R. cordifolia has been studied in rat liver homogenate. It prevents the cumene hydroperoxide induced malondialdehyde formation in the dose and time dependent manner. This effect is accompanied by the maintained reduced glutathione level even in the presence of above toxin.

Involvement of tyrosine kinase and protein kinase C in platelet-activating-factor-induced c-fos gene expression in A-431 cells.

In A-431 cells, platelet-activating factor (PAF) induces the expression of c-fos and TIS-1 genes in both the absence and the presence of cycloheximide in a structurally specific and receptor-coupled manner. We have now investigated the molecular mechanisms of this response, particularly in relation to the role of protein kinases. Pretreatment of cells with genistein or methyl-2,5-dihydroxycinnamate (tyrosine kinase inhibitors) or staurosporine (a protein kinase C inhibitor) for 20 min abolished the c-fos expression induced by PAF. Interestingly, when genistein was added 90 s after addition of PAF, no inhibition was observed. Similarly, staurosporine did not inhibit c-fos expression when added 8 min after PAF addition to the cells. These inhibitions were dose-dependent (IC50 for staurosporine was 180 nM, and for genistein 50 microM). Simultaneous addition of PAF and phorbol 12-myristate 13-acetate (PMA) did not give a synergistic effect on c-fos expression. Pretreatment of cells with PMA had no effect on [3H]PAF binding, but abolished the PAF-induced gene expression. PAF-stimulated gene expression was desensitized if cells were pretreated with PAF. Interestingly, epidermal growth factor was able to stimulate c-fos expression in PAF-desensitized cells, and thus indicated involvement of distinct mechanisms for the two stimuli. Forskolin, an activator of adenylate cyclase, did not induce c-fos expression and had no effect on the PAF response. Exposure of cells to PAF for as little as 1 min, followed by its removal, was sufficient to activate the gene expression and demonstrated the rapidity and the exquisite nature of the signalling involved in this process. It is concluded that activation of PAF receptor (a proposed G-protein-coupled receptor) causes rapid production of signals which induce the expression of c-fos gene and that this is mediated via tyrosine kinase and protein kinase C.

Platelet activating factor induces expression of early response genes c-fos and TIS-1 in human epidermoid carcinoma A-431 cells.

The effect of platelet activating factor (PAF) on the induction of early response genes was investigated in A-431 cells (human epidermal carcinoma cells). PAF induced a transient expression of c-fos and TIS-1 mRNA in a time- and dose-dependent manner. As low as 10(-10) M PAF caused detectable expression of these genes with a maximum observed at 10(-7) M. In the presence of cycloheximide, increases in the gene expression were noticeable at 20 min and peaked between 30-60 min. A lack of induction with lyso-PAF, an inactive PAF metabolite, confirmed the specificity of PAF towards this expression. The cells pretreated with CV-6209, a PAF receptor antagonist, did not show any induction of these genes by PAF. It is concluded that PAF causes induction of the early response genes c-fos and TIS-1 in a structurally specific and receptor dependent manner. This finding offers a new role for PAF at the nuclear level and may have important implications in the long term effects of PAF in pathophysiological conditions.