The scientific basis of rasa (taste) of a substance as a tool to explore its pharmacological behavior.

BACKGROUND: A rational and well-developed pharmacological basis forms the foundation of therapeutics in Ayurveda. The principles and theories of Ayurveda need to be validated in the scientific context in order to harness the millennia old knowledge. Rasa (taste) of the substance is the foremost tool in Ayurveda to assess and determine the pharmacological properties and actions of the substance. Similarity in rasa is said to signify similar structure and consequently similar pharmacological behavior. Depending on skills developed over the course of long-term clinical experience one, can register the minute variations in rasa of substances and accordingly the possible variations in pharmacological actions. Thus, rasa can be used as a scientific tool in the drug discovery process to limit and focus the target areas. AIM: To sensitize scientific community to the utility of rasa as a tool in the process of drug discovery. MATERIALS AND METHODS: All relevant ancient and contemporary literature was reviewed critically to form a scientific basis of the Ayurvedic concept of rasa as a tool to identify the pharmacological behavior of a substance. CONCLUSION: The review finds that rasa (taste) can be used as a guide to identify potential targets in drug discovery.

A critical review of rhythmic recitation of Charakasamhita as per Chhanda Shastra.

Charakasamhita is one of the most important life lines of Ayurvedic classical knowledge. This supreme text of "science of life" has been composed nearly about 3000 years ago and before the well-established era of documentation. It is composed in the then language, style, and method. The ancient scholars of Ayurveda have presented it in such a way that all three kinds of pupil can get the matter easily. Nearly two thirds of the compendium is shaped in verse form according to rules and regulations of Chhandashastra of classical Sanskrit literature to retain in memory for a long time. With the advent of time this classical practice of recitation has been gradually losing its popularity and as a result the proper Ayurvedic learning cannot be completely possible in the current era. This review consists of methods of rhythmic recitation of all verses of Charakasamhita with notations and classical analysis.

Clinical evaluation of root tubers of Shweta Musali (Chlorophytum borivilianum L.) and its effect on semen and testosterone.

Shweta Musali (Chlorophytum borivilianum (CB)) is a traditionally used herb for its benefits in male sexual and general health. In the recent past, the herb has attained much commercial significance, both in domestic and international markets. However, limited clinical data is available to establish its traditional claims. The present study was aimed at evaluating the effect of the water soluble extract of CB root tubers on semen and testosterone in healthy adult males. The research was designed as a randomized, double-blind, placebo-controlled, trial upon the volunteers registered from the outpatient department (OPD) with age ranging from 20 to 40 years. Water extracts of CB and placebo was administered in the patients of groups A and B, for 12 weeks, in two divided doses of 500 mg. Assessment was done based upon Semen (Volume, Liquefaction Time, Sperm Count, Sperm motility) and Serum Testosterone levels parameters. Highly significant improvement was noted in the above parameters after administration of CB extract in comparison to Placebo. Hence it was concluded that the trial drug was effective in improving male sexual health.

A comprehensive outlook of Sannipata.

Nomenclature of the disease on the basis of vitiation of the body humors is stressed in ayurveda. Sannipatika, i.e., 'conglomeration of vitiated tridosa' is the final stage of process of manifestation of disease. In this specific state of pathogenesis, the disease becomes more advance and mostly irreversible. A detailed scientific study of Sannipatika-avastha has been documented in classics. Comprehensive analysis of sannipata-state and its ways of presentation is the main theme of the current article.

A critical review of the philosophical concepts of Carakopaskara commentary.

Philosophy is the prime specialty as it fulfills the ultimate goal of life with the depiction of the liberation of the soul. The human body composed of mind, other sensory organs along with five proto-elements, is to be treated from the clinical applicability of the philosophical series of events. The current review is the categorical analysis of the philosophical thought depicted in "Carakopaskara commentary" of Pandit Jogindranath Sen in the purview of underlined theme of Caraka Samhita and classical orthodox philosophy.

Human intestinal intraepithelial lymphocytes and epithelial cells coinduce interleukin-8 production through the CD2-CD58 interaction.

Human intestinal CD3+TCRalphabeta+CD8+ intraepithelial lymphocytes (IELs) are intimately associated with epithelial cells (ECs) through binding of CD103 to E-cadherin. How these two cell types functionally interact is largely unknown. IEL-EC cross talk was determined using HT-29 cells as the model EC and IL-8 as the readout. IL-8 was derived from both cell types and synergistically increased when the cells were combined. This synergistic effect required active transcription by both IELs and HT-29 cells. Cell contact was required as shown by the loss of the synergistic increase in IL-8 when the two cell types were separated by Transwells. Specifically, IL-8 release required the binding of CD2 on the IELs to CD58 on the HT-29 cells. The association of the CD3/TCR complex with major histocompatibility antigen class I antigens was not involved. Antibody neutralization of tumor necrosis factor-alpha (TNF-alpha), but not interferon-gamma (IFN-gamma), resulted in increased IL-8 production by the coculture. Although both TNF-alpha and IFN-gamma increased IL-8 synthesis and CD58 expression by the HT-29 cells, only IFN-gamma reduced IL-8 production by IELs. IL-8 production by either cell type involved phosphorylation of p38 and JNK. In summary, the synergistic synthesis of IL-8 occurs when IELs are stimulated through the CD2 pathway by CD58 on HT-29 cells, resulting in TNF-alpha release that, in turn, augments IL-8 synthesis and CD58 expression by the HT-29 cells.

Evidence for alteration in chemical and physical properties of water and modulation of its biological functions by sunlight transmitted through color ranges of the visible spectrum-a novel study.

We investigated the changes in the properties of water when exposed to sunlight for 40 days. We hypothesize and prove that solar irradiation to water entraps electromagnetic radiation as potential energy, which becomes kinetic energy in various systems. It is postulated that photochemically-induced energy transfers, associated with individual spectral emission of visible spectrum of solar light, exert diverse influences on biological systems. Bottles of distilled water, individually wrapped in spectral-colored cellophane were exposed to sunlight and compared to an unwrapped bottle to determine chemical and physical changes as well as modifications of biological properties. Each bottle of water was named according to the color of cellophane paper with letter E (stands for exposed) as a prefix with (E-violet, E-indigo, E-blue, E-green, E-yellow, E-orange, and E-red). E-control (without wrap) was exposed to polychromatic sunlight. This study addresses two main issues viz., the chemical and physical changes in E-water and its effect on biological activities. Chemical and physical composition analysis using inductively coupled plasma atomic emission spectrometry; physical conductance by a Wheatstone Bridge type conductivity meter; osmolarity by a vapor pressure osmometer; and, salt solubility profile of 10% sodium bicarbonate were determined. Furthermore, testing the effect of E-waters on human lymphocyte proliferation, mosquito larvae hatching and seed germination determined the functional role of solar radiation through specific spectrum/s of visible light on various biological processes. We found that water exposed to visible spectral emissions of sunlight had an altered elemental composition, electrical conductance, osmolarity and salt-solubility, as well as differences in bio-modulatory effects. A gradual increase in leaching of Boron from E-violet to E-red was noted. E-indigo showed maximal increase in electrical conductance and maximal salt solubility of sodium bicarbonate. E-blue inhibited phyto-hemagglutinin-induced immune cell proliferation and mosquito larvae hatching. E-orange stimulated root elongation in seed germination. We conclude that 40-day exposure of water to specific solar spectrum changes chemical and physical properties and influences on biological activity.

Immunological findings in autism.

The immunopathogenesis of autism is presented schematically in Fig. 1. Two main immune dysfunctions in autism are immune regulation involving pro-inflammatory cytokines and autoimmunity. Mercury and an infectious agent like the measles virus are currently two main candidate environmental triggers for immune dysfunction in autism. Genetically immune dysfunction in autism involves the MHC region, as this is an immunologic gene cluster whose gene products are Class I, II, and III molecules. Class I and II molecules are associated with antigen presentation. The antigen in virus infection initiated by the virus particle itself while the cytokine production and inflammatory mediators are due to the response to the putative antigen in question. The cell-mediated immunity is impaired as evidenced by low numbers of CD4 cells and a concomitant T-cell polarity with an imbalance of Th1/Th2 subsets toward Th2. Impaired humoral immunity on the other hand is evidenced by decreased IgA causing poor gut protection. Studies showing elevated brain specific antibodies in autism support an autoimmune mechanism. Viruses may initiate the process but the subsequent activation of cytokines is the damaging factor associated with autism. Virus specific antibodies associated with measles virus have been demonstrated in autistic subjects. Environmental exposure to mercury is believed to harm human health possibly through modulation of immune homeostasis. A mercury link with the immune system has been postulated due to the involvement of postnatal exposure to thimerosal, a preservative added in the MMR vaccines. The occupational hazard exposure to mercury causes edema in astrocytes and, at the molecular level, the CD95/Fas apoptotic signaling pathway is disrupted by Hg2+. Inflammatory mediators in autism usually involve activation of astrocytes and microglial cells. Proinflammatory chemokines (MCP-1 and TARC), and an anti-inflammatory and modulatory cytokine, TGF-beta1, are consistently elevated in autistic brains. In measles virus infection, it has been postulated that there is immune suppression by inhibiting T-cell proliferation and maturation and downregulation MHC class II expression. Cytokine alteration of TNF-alpha is increased in autistic populations. Toll-like-receptors are also involved in autistic development. High NO levels are associated with autism. Maternal antibodies may trigger autism as a mechanism of autoimmunity. MMR vaccination may increase risk for autism via an autoimmune mechanism in autism. MMR antibodies are significantly higher in autistic children as compared to normal children, supporting a role of MMR in autism. Autoantibodies (IgG isotype) to neuron-axon filament protein (NAFP) and glial fibrillary acidic protein (GFAP) are significantly increased in autistic patients (Singh et al., 1997). Increase in Th2 may explain the increased autoimmunity, such as the findings of antibodies to MBP and neuronal axonal filaments in the brain. There is further evidence that there are other participants in the autoimmune phenomenon. (Kozlovskaia et al., 2000). The possibility of its involvement in autism cannot be ruled out. Further investigations at immunological, cellular, molecular, and genetic levels will allow researchers to continue to unravel the immunopathogenic mechanisms' associated with autistic processes in the developing brain. This may open up new avenues for prevention and/or cure of this devastating neurodevelopmental disorder.

Regulation of the intestinal epithelial response to cyclic strain by extracellular matrix proteins.

Repetitive mechanical deformation may stimulate intestinal epithelial proliferation. Because the extracellular matrix modulates static intestinal epithelial biology, we examined whether matrix proteins influence intestinal epithelial responses to deformation. Human Caco-2BBE cells and nontransformed human enterocytes (HIPEC) were subjected to 10% average cyclic strain at 10 cycles/min on flexible membranes precoated with matrix proteins without or with plasma fibronectin or functional anti-integrin antibodies in the medium. Strain stimulated proliferation, focal adhesion kinase, extracellular signal-regulated protein kinase (ERK), p38, and Jun N-terminal kinase similarly on collagen I or IV, and more weakly on laminin, but had no effect on fibronectin. MEK blockade (PD98059) prevented strain-stimulated proliferation on collagen but did not affect proliferation on fibronectin. Adding tissue fibronectin to a collagen substrate or plasma fibronectin to the media suppressed strain s mitogenic and signal effects, but not those of epidermal growth factor. Functional antibodies to the alpha5 or alpha(v) integrin subunit blocked strain's effects on Caco-2 proliferation and ERK activation, although ligation of the alpha2 or alpha6 subunit did not. Repetitive strain also stimulated, and fibronectin inhibited, human intestinal primary epithelial cell proliferation. Repetitive deformation stimulates transformed and nontransformed human intestinal epithelial proliferation in a matrix-dependent manner. Tissue or plasma fibronectin may regulate the intestinal epithelial response to strain via integrins containing alpha5 or alpha(v).

Responsiveness of intestinal epithelial cell lines to lipopolysaccharide is correlated with Toll-like receptor 4 but not Toll-like receptor 2 or CD14 expression.

BACKGROUND AND AIMS: Luminal bacteria have been implicated in the pathogenesis of inflammatory bowel diseases. Exposure of intestinal epithelial cells (IEC) to bacterial components potentially initiates intestinal inflammation by release of chemokines and recruitment of inflammatory cells. We analyzed receptor expression and signaling pathways involved in activation of human primary IEC and carcinoma-derived cell lines by lipopolysaccharide (LPS). MATERIALS AND METHODS: HT-29/p, HT-29/MTX, and Caco-2 cells were stimulated by LPS. IL-8 content in supernatants was analyzed by ELISA, and expression of CD14, Toll-like receptor (TLR) 2 and TLR 4 was determined by RT-PCR. Presence of TLR 4 protein was assessed by western blot analysis. LPS response was modulated by sCD14, LPS-binding protein, neutralization of CD14, and inhibitors of early signal activation. RESULTS: LPS dose-dependently induced secretion of IL-8 in undifferentiated HT-29/p cells while Caco-2 and permanently differentiated HT-29/MTX cells were unresponsive. Differently to HT-29/MTX, both HT-29/p and Caco-2 cells constitutively expressed transcripts for CD14. However, CD14 was not required for LPS-mediated induction of IL-8 in HT-29/p cells since neutralizing anti-CD14 antibodies left IL-8 levels unchanged. Unresponsiveness of Caco-2 and HT-29/MTX cells to LPS persisted in the presence of sCD14 and/or LPS-binding protein. Neither cell line expressed TLR 2 transcripts while only responsive HT-29/p cells expressed TLR 4 mRNA and TLR 4 protein. Butyrate down-regulated TLR 4 expression and significantly diminished LPS-dependent IL-8 secretion. Inhibition of G protein dependent kinase activation reduced IL-8 levels to 50%; the phosphatidyl-inositol-3'-kinase inhibitor LY294002 abrogated the response. CONCLUSION: Responsiveness of IEC lines to LPS is positively correlated with TLR 4 expression. Strategies targeting TLR 4 expression or TLR 4 mediated signaling may antagonize IEC activation by LPS.

Cytokine regulation of human intestinal primary epithelial cell susceptibility to Fas-mediated apoptosis.

The regulatory mechanisms of nontransformed intestinal epithelial cell apoptosis have not been thoroughly investigated. We determined the susceptibility and mechanism of Fas-mediated apoptosis in nontransformed human intestinal epithelial cells (HIPEC) in the presence and absence of inflammatory cytokines. Despite ample expression of Fas, HIPEC were relatively insensitive to Fas-mediated apoptosis in that agonist anti-Fas antibody (CH11) induced a <25% increase in HIPEC apoptosis. Pretreatment of HIPEC with interferon (IFN)-gamma, but not tumor necrosis factor-alpha or granulocyte-macrophage colony-stimulating factor, significantly increased CH11-induced apoptosis of these cells without increasing Fas expression. Increased apoptosis correlated with increased caspase 3 activation but not expression of procaspase 3. Also, there was a significant delay in the onset of Fas-mediated apoptosis in HIPEC, which correlated with the generation of an activated caspase 3 p22/20 subunit. HIPEC required both initiator caspases 8 and 9 activity but expressed significantly less of the zymogen form of these caspases than did control cells. IFN-gamma-mediated sensitization of HIPEC occurred upstream of caspase 9 activation and correlated with a small increase in procaspase 8 expression (<1-fold increase) and a significant increase in expression of an intermediate form (p35) of caspase 4 (3.3-fold increase).