Effect of ethanolic extract of Rosa centifolia against doxorubicin induced nephrotoxicity in albino rats.

BACKGROUND: Efficacy of Anthracycline derivative Doxorubicin (Dox) has been proven in several malignancies such as breast cancer, Hodgkin and non-Hodgkin lymphoma, acute leukemia, lung, thyroid and ovarian cancer. However its clinical usefulness is restricted due to its cardiotoxicity and nephrotoxicity. Rosa centifolia belongs to family Rosaceae and in Ayurveda it is claimed for use in renal disorders. The main phyto-constituents of the plant are terpenoids, glycosides, flavonoids, tannins, phenolic compounds, pro-antroocyanides, pectin and riboflavin. OBJECTIVE: To investigate the ameliorative role of ethanolic extract of petals of R. centifolia in doxorubicin induced nephrotoxicity in rats. MATERIALS AND METHODS: Nephrotoxicity was produced by administration of doxorubicin (2.5 mg/kg b.w., i.p. alternate day) in six equal injections for two weeks to achieve a cumulative concentration of 15 mg/kg. Low (LERC - 100 mg/kg p.o.) and high (HERC - 200 mg/kg p.o.) dosees of ethanolic extract of petals of R. centifolia was administered as a pretreatment prior to doxorubicin administration. The general parameters such as body weight, food and water intake were measured throughout the study period. Serum biomarkers such as blood urea nitrogen (BUN), serum creatinine and albumin were measured before treatment and at the end of the experiments. Anti-oxidant enzymes such as glutathione (GSH), melonldehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) were monitored after the last dose. Nephrotoxicity was assessed through histopathological analysis. RESULTS: The repeated administration of doxorubicin produces several morphological changes including reduction in the body weight as well as decreased food and water consumption. Serum biomarkers such as BUN, serum creatinine were increased and albumin concentration was decreased. The GSH, SOD and CAT concentrations were decreased, whereas MDA concentration was increased. Deteriorating changes in the histological architecture of kidney tissue were observed. In the LERC and HERC pretreated groups following changes were observed in dose dependent manner: increase in body weight, food and water intake (p < 0.05 and p < 0.01), decrease in the BUN (p < 0.05 and p < 0.01) and serum creatinine (p < 0.05 and p < 0.05) concentrations respectively. The significant increase in the albumin (p < 0.01) concentration was observed only in HERC. The pretreatment with LERC and HERC increased the antioxidant enzymes concentrations i.e. GSH (p < 0.01 and p < 0.01), SOD (p < 0.01 and p < 0.01), CAT (p < 0.05 and p < 0.01) and decreased the MDA concentration (p < 0.05 and p < 0.01) respectively. Histopathological studies showed that the pretreatment with low and high doses of ethanolic extract of petals of Rosa centifolia LERC and HERC groups minimized the tubular damage and reduced the inflammation as compared to doxorubicin treated group. CONCLUSION: The biochemical and histopathological data from the present study clearly support the nephroprotective effect of ethanolic extract of petals of R. centifolia, which might be credited to its anti-oxidant property.

Anti-inflammatory and antioxidant effect of Kerabala: a value-added ayurvedic formulation from virgin coconut oil inhibits pathogenesis in adjuvant-induced arthritis.

Kerabala (CB) is a novel ayurvedic formulation used for treating various inflammatory diseases. This formulation was made from virgin coconut oil and it comprises extracts of Sida cordifolia, coconut milk and sesame oil. The current study was performed to evaluate the anti-inflammatory action of CB on carrageenan-induced acute and adjuvant-induced chronic experimental models. 5 mg/kg bwt was found to be potent dose from carrageenan model and evaluated its effect in adjuvant-induced chronic arthritic model. The antioxidant assays like SOD, catalase, glutathione peroxidase, lipid peroxidation product, nitrate level and GSH were measured in paw tissue. Hematological parameters like hemoglobin (HB) count, ESR, WBC count, plasma CRP levels were analyzed. By RT-PCR, the inflammatory markers like cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) expressions were evaluated. The extracellular matrix proteins like MMP-2 and MMP-9 were determined by zymography and its expression by western blotting. Histopathology and cytology of paw tissue and synovium were analyzed. The result indicated that there was a significant increment in the levels of antioxidant enzymes on CB administration. The hematological markers such as ESR, WBC and plasma CRP levels were reduced by CB treatment and it also increases the HB level. The upregulated gene level expressions of inflammatory markers like COX-2, iNOS, TNF-α and IL-6 were down regulated by administration of CB. MMP-2 and MMP-9 expression significantly reduced by CB administration. Massive influx of inflammatory cell infiltration, proliferative collagen in histological analysis of paw tissue of arthritic rat was decreased by CB administration. Synovial cytology of CB administrated group shows reduced number of reactive mesothelial cells and synovial inflammatory cells. This current study shows that ayurvedic drug CB has an antioxidant, anti-inflammatory and anti-arthritic activity in experimental arthritic model. CB as an anti-arthritic drug has beneficial effect for treating inflammation, tissue damage and pain associated with arthritis.

Physico-Chemical profile of Puga Khanda: A Preliminary Study.

BACKGROUND: Herbal medicines are the oldest known form of medicine in the world. However, the quality control and the assurance still remains a challenge because of the high variability of chemical components. Herbal drugs, singlely or in combinations, contain numerous compounds in complex matrices in which no single active constituent is responsible for the overall efficacy. This creates a challenge in establishing quality control standards and the standardization of finished herbal products. Many formulations have been mentioned in Ayurvedic text for Vrushyatwa (aphrodisiac). Puga Khanda is one among such formulations. AIM: To develop preliminary physico-chemical profile of Puga Khanda. MATERIALS AND METHODS: Puga Khanda was prepared in three batches as per the classical reference mentioned in Bhaishajya Ratnavali. The formulation was subjected for physico-chemical analysis, phytochemical analysis and Thin Layer Chromatography (TLC). RESULTS AND CONCLUSION: The study revealed that organoleptic characters, pH and extractive values of all 3 samples were almost equal. All the samples had 60% of sugar needed for preservation and 2/3(rd) of it was non reducing sugar. The total alkaloids ranged from 0.002 to 0.004% w/w. In TLC study the entire samples showed similar pattern except the 2(nd) sample of Puga Khanda.

Polyphenolics isolated from virgin coconut oil inhibits adjuvant induced arthritis in rats through antioxidant and anti-inflammatory action.

We evaluated the protective efficacy of the polyphenolic fraction from virgin coconut oil (PV) against adjuvant induced arthritic rats. Arthritis was induced by intradermal injection of complete Freund's adjuvant. The activities of inflammatory, antioxidant enzymes and lipid peroxidation were estimated. PV showed high percentage of edema inhibition at a dose of 80mg/kg on 21st day of adjuvant arthritis and is non toxic. The expression of inflammatory genes such as COX-2, iNOS, TNF-α and IL-6 and the concentration of thiobarbituric acid reactive substance were decreased by treatment with PV. Antioxidant enzymes were increased and on treatment with PV. The increased level of total WBC count and C-reactive protein in the arthritic animals was reduced in PV treated rats. Synovial cytology showed that inflammatory cells and reactive mesothelial cells were suppressed by PV. Histopathology of paw tissue showed less edema formation and cellular infiltration on supplementation with PV. Thus the results demonstrated the potential beneficiary effect of PV on adjuvant induced arthritis in rats and the mechanism behind this action is due to its antioxidant and anti-inflammatory effects.

A novel human TPIP splice-variant (TPIP-C2) mRNA, expressed in human and mouse tissues, strongly inhibits cell growth in HeLa cells.

Alternative splicing of mRNAs is known to involve a major regulation of gene expression at RNA level in mammalian cells. The PTEN (Phosphatase and TENsin homologue deleted from the human chromosome 10), TPTE (Transmembrane Phosphatase with TEnsin homology) and TPIP (TPTE and PTEN homologous Inositol lipid Phosphatase) belong to a family of dual-specific lipid and protein phosphatases. PTEN is a well characterized tumor suppressor, which plays crucial role in cell survival, cell cycle regulation, cell proliferation as well as adhesion, motility and migration of cells. The C2-domain of PTEN is essential for PTEN-functions. We have isolated a novel 1019 bp human TPIP cDNA (TPIP-C2) from a human testis cDNA library. In silico analysis of the cDNA revealed that it is produced from the TPIP-locus on the human chromosome 13 by alternative RNA-splicing. It has a unique 5'-Alu sequence, a LINE sequence followed by a 582 bp Open Reading Frame (ORF) encoding a 193 aa polypeptide with a partial phosphatase domain and a C2-domain. TPIP-C2 mRNA is expressed in human testis and in mouse tissues. Mouse testis and brain showed higher levels of TPIP-C2 mRNA in comparison to the heart, liver and kidney under normal physiological conditions. TPIP-C2 mRNAs from human and mouse testes show extensive sequence identity. Over-expression of TPIP-C2 cDNA in HeLa cells strongly (up to 85%) inhibited cell growth/proliferation and caused apoptosis in a caspase 3-dependent manner. These findings suggest for the first time that a TPIP splice-variant mRNA with a partial phosphatase domain and a C2-domain is expressed in cells and tissues of human and murine origins under normal physiological conditions. Inhibition of cell growth/proliferation and induction of apoptosis by overexpression of TPIP-C2 mRNA in HeLa cells suggest that it may be involved in negative regulation of cell growth/proliferation.

Standardization and quality control parameters of Dashanga Kwatha ghana tablet: An Ayurvedic formulation.

Herbal medicines have a long therapeutic history and are still serving many of the health needs of a large population of the world. However, the quality control and quality assurance still remains a challenge because of the high variability of chemical components involved. Herbal drugs, singularly and in combinations, contain numerous compounds in complex matrices in which no single active constituent is responsible for the overall efficacy. This creates a challenge in establishing quality control standards and standardization of finished herbal drugs. Many preparations have been mentioned in Ayurvedic text books for the treatment of Urdhwaga Amlapitta (non-ulcer dyspepsia). Dashanga Kwatha is one such known formulation. In this study, Dashanga Kwatha was converted into tablet form to increase the shelf life, make it easy to dispense, for dose fixation, etc. The Dashanga Kwatha Ghana tablet was subjected to organoleptic analysis, phytochemical analysis, and qualitative analysis to detect the presence of various functional groups, and to high performance thin layer chromatography (HPTLC) examination by optimizing the solvent systems. The investigation revealed the presence of tannins, mucilage, ascorbic acid, alkaloids, saponins, glycosides, flavonoids and carbohydrates mainly.

Neutraceuticals in Ayurveda with special reference to Avaleha Kalpana.

The use of Neutraceuticals has drastically risen in recent years. Dr Stephan De Felice coined the term Neutraceuticals from "nutrition" and "pharmaceutical" in 1989. Related terms are "functional food" and "dietary supplement". In Ayurvedic pharmaceutics there are some secondary preparations like Avaleha Kalpana (Medicated semisolid preparation), Asavarista Kalpana (fermented preparation), Sneha Kalpana (Medicated fatty preparation), Ksheerapaka Kalpana (Medicated milk preparation) etc. which can be correlated with Neutraceuticals. In this paper "Neutraceuticals" and "Avaleha Kalpana" have been correlated and discussed.

Roots of Withania somnifera Inhibit Forestomach and Skin Carcinogenesis in Mice.

We evaluated the cancer chemopreventive efficacy of the Withania somnifera root, which has been used in the Indian traditional medicine system for many centuries for the treatment of various ailments. Since, studies showing its mechanism-based cancer chemopreventive efficacy are limited, this was investigated in the present study. We studied the effect of dietary administration of Withania root on hepatic phase I, phase II and antioxidant enzymes by estimation of its level/activity, as well as in attenuating carcinogen-induced forestomach and skin tumorigenesis in the Swiss albino mouse model. Our findings showed that roots of W.somnifera inhibit phase I, and activates phase II and antioxidant enzymes in the liver. Further, in a long-term tumorigenesis study, Withania inhibited benzo(a)pyrene-induced forestomach papillomagenesis, showing up to 60 and 92% inhibition in tumor incidence and multiplicity, respectively. Similarly, Withania inhibited 7,12-dimethylbenzanthracene-induced skin papillomagenesis, showing up to 45 and 71% inhibition in tumor incidence and multiplicity. In both studies, Withania showed no apparent toxic effects in mice as monitored by the body weight gain profile. Together, these findings suggest that W.somnifera root has chemopreventive efficacy against forestomach and skin carcinogenesis and warrants the identification and isolation of active compounds responsible for its anticancer effects, which may provide the lead for the development of antitumor agents.

Chemoprevention by Hippophae rhamnoides: effects on tumorigenesis, phase II and antioxidant enzymes, and IRF-1 transcription factor.

Fruits or berries of Hippophae rhamnoides (sea buckthorn), a rich source of vitamins A, C, and E, carotenes, flavonoids, and microelements such as sulfur, selenium, zinc, and copper, are edible and have been shown to protect from atopic dermatitis, hepatic injury, cardiac disease, ulcer, and atherosclerosis. However, its mechanism of action is not clear. We show that Hippophae inhibits benzo(a)pyrene-induced forestomach and DMBA-induced skin papillomagenesis in mouse. This decrease in carcinogenesis may be attributed to the concomitant induction of phase II enzymes such as glutathione S-transferase and DT-diaphorase and antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the mouse liver. This was accompanied by a remarkable induction of the transcription factor interferon regulatory factor-1 in the Hippophae-treated liver. Our results strongly suggest that Hippophae fruit is able to decrease carcinogen-induced forestomach and skin tumorigenesis, which might involve up-regulation of phase II and antioxidant enzymes as well as DNA-binding activity of IRF-1, a known antioncogenic transcription factor causing growth suppression and apoptosis induction for its anticancer effect.