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.

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.

Scoping review on the role and interactions of hydroxytyrosol and alpha-cyclodextrin in lipid-raft-mediated endocytosis of SARS-CoV-2 and bioinformatic molecular docking studies.

OBJECTIVE: The aim of the study was to show the effect that two naturally occurring compounds, a cyclodextrin and hydroxytyrosol, can have on the entry of SARS-CoV-2 into human cells. MATERIALS AND METHODS: The PubMed database was searched to retrieve studies published from 2000 to 2020, satisfying the inclusion criteria. The search keywords were: SARS-CoV, SARS-CoV-2, coronavirus, lipid raft, endocytosis, hydroxytyrosol, cyclodextrin. Modeling of alpha-cyclodextrin and hydroxytyrosol were done using UCSF Chimera 1.14. RESULTS: The search results indicated that cyclodextrins can reduce the efficiency of viral endocytosis and that hydroxytyrosol has antiviral properties. Bioinformatic docking studies showed that alpha-cyclodextrin and hydroxytyrosol, alone or in combination, interact with the viral spike protein and its host cell receptor ACE2, thereby potentially influencing the endocytosis process. CONCLUSIONS: Hydroxytyrosol and alpha-cyclodextrin can be useful against the spread of SARS-CoV-2.

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.

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.

Assessment of the adrenergic beta-blocking activity of Inula racemosa.

Inula racemosa root powder was investigated in patients with proven ischaemic heart disease. The powder prevented ST-segment depression and T-wave inversion as observed in the post-exercise electrocardiogram. The petroleum ether extract of roots lowered plasma insulin and glucose levels within 75 min of oral administration to albino rats and it significantly counteracted adrenaline-induced hyperglycaemia in rats. The extract further showed negative inotropic and negative chronotropic effects on frog heart. All these findings indicate that one of the constituents of Inula racemosa may have adrenergic beta-blocking activity.

Molecular approach to ayurveda.

In ayurvedic system of medicine, it is considered that a living system is made of panch-mahabuta, in the form of Vata, pitta and kapha at the physical level and satwa, raja and tama at the mental level. This covers the psychosomatic constitution and commonly known as the Tridosh theory. The imbalance in these body humours is the basic cause of any type of disease manifestation. Till date, several objective parameters have been proposed to monitor the level of these basic humours but none of them is complete. In this exercise, now it is proposed to consider free radical theory of diseases as one of the objective parameters. To be more specific, vata can be monitored in terms of membrane bound signal transduction, pitta as the process of phosphorylation and de-phosphorylation of different proteins (signalling moieties and enzymes) and kapha can be viewed as the degree of gene expression as protein synthesis. This can be correlated with the ojas of the body or total body defence mechanism.

Role of Tamra bhasma, an Ayurvedic preparation, in the management of lipid peroxidation in liver of albino rats.

Hepatoprotective effect of Tamra bhasma has been studied on cumene hydroperoxide (CHP) induced peroxidation, reduced glutathione content and superoxide dismutase (SOD)-in rat liver homogenate. The drug was orally given for 8 days which showed significant reduction in the level of malondialdehyde (MDA) production at different concentrations of cumene hydroperoxide in vitro. Glutathione content was maintained upto seventy minutes and SOD activity was enhanced to 166%. These animals did not show any rise in serum GOT and GPT. On similar doses no histological changes were observed in liver. The results suggested that Tamra bhasma is a strong antioxidant drug and could be used in the management of lipid peroxidation with no detectable adverse effect.

Semecarpus anacardium L, nuts inhibit lipopolysaccharide induced NO production in rat macrophages along with its hypolipidemic property.

Traditionally S. anacardium is used for rejuvenation, rheumatoid arthritis, fever and neurological disorders. In the present study it was observed that a fraction of S. anacacrdium at dose of 1 mg/100 g body wt, significantly reduced serum cholesterol from 378.87 mg/dl in the rats fed with atherogenic diet (AD) to 197.99 mg/dl (45-52%) in the rats fed with AD diet and increased serum HDL-cholesterol (33-37%). The same fraction also inhibited LPS induced NO production in the culture activated rat peritoneal macrophages in the dose dependent manner with IC50 value at 50 ng/ml of the culture medium. The drug in the above doses was completely safe and non-toxic, (no change in the enzymes), to liver and kidney functions.

Assessment of endocrine response of Inula racemosa in relation to glucose homeostasis in rats.

Alcoholic extract of the root of I. racemosa lowers blood glucose and enhances liver glycogen without increasing plasma insulin in rats. There is also no increase in degree of degranulation of the beta cells of pancreas. In similar conditions it does not show any effect on activity of adrenal gland. However, thyroid gland undergoes activation at the later stage (delayed response). It appears that hypoglycemic response of I. racemosa is not due to enhanced secretion/synthesis of insulin; the action may be at the peripheral level by potentiating the insulin sensitivity.

Role of alcoholic extract of shoot of Hypericum perforatum Linn on lipid peroxidation and various species of free radicals in rats.

The alcoholic extract of the shoot of H. perforatum shows strong antioxidant property. It possesses the iron chelation property with more affinity to the ferrous form. It has scavenging property for both superoxide and for hydroxyl radicals but the response is more towards the superoxide radicals. Thus in addition to the anti-depressant property it has strong antioxidant property also.

Effect of Semecarpus anacardium nuts on lipid peroxidation.

Alcoholic extract of pericarp showed significant protection against FeSO4 induced lipid peroxidation, as compared with whole native nut and seeds. Mechanism of action may be through metal chelation or activation of endogenous antioxidant enzymes, because the extract did not show hydroxyl and super oxide anion scavenging property. Further in vitro experiments against FeSO4, it did not maintain the level of reduced glutathione.

Antilipid peroxidative property of Nardostachys jatamanasi.

Antiperoxidative property of N. jatamanasi was tested by using iron induced lipid peroxidation in 5% rat liver homogenate. The degree of peroxidation was quantitated by thiobarbituric acid reactive substance (TBARS) content. The extract provided protection against lipid peroxidation. The hexane fraction was more potent than the alcoholic extract. Results suggested antilipid peroxidative property of the plant.

Antioxidant property of Smilex china Linn.

Smilex china Linn. (Smilacaceae Syn Liliaceae) has special pharmacognostic feature as its root is multiseriate, with sclerenchymatic pericycle. The alcoholic extract of rhizome of S. china shows significant protection against FeSO4 induced lipid peroxidation in rat liver homogenate, but has no effect on the rate of oxidation of reduced glutathione. This fraction scavenges the superoxide and hydroxyl radicals, but the effect was more towards the removal of superoxide than that of hydroxyl radicals. Thus it could be concluded that rhizome of S. china has strong antioxidant property.

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.

Anti-platelet activating factor property of Rubia cordifolia Linn.

Rubia cordifolia is clinically used for the purification of blood by the physicians of the Indian System of Medicine. For the first time, the effect of the partially purified fraction of this whole plant has been studied on rabbit platelets. It inhibits the platelet aggregation induced by PAF (platelet activating factor) but not thrombin. It also inhibits the binding of 3H-PAF to the platelets in the dose-dependent manner. Thus it appears that R. cordifolia inhibits action of PAF at its receptor level either by it's blocking or by desensitization.

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.

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.

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.