Kiranjeet Kour

Restoration of stress-induced altered T cell function and corresponding cytokines patterns by Withanolide A

This study was taken up to see the effect of Withanolide A (WS-1), a compound isolated from Withania somnifera root extract on chronic stress-induced alterations on T lymphocyte subset distribution and corresponding cytokine secretion patterns in experimental Swiss albino mice. Stress disturbs the homeostatic state of the organism and brings about behavioral, endocrine and immunological changes. The chronic suppression induced by stress depresses the immune functioning and increases susceptibility to diseases. Oral administration of WS-1 once daily at the graded doses of 0.25, 0.5, 1 and 2 mg/kg p.o. caused significant recovery of stress-induced depleted T cell population causing an increase in the expression of IL-2 and IFN-gamma (a signature cytokine of Th1 helper cells) and a decrease in the concentration of corticosterone in stressed experimental animals. It also reversed the restraint stress-induced increase in plasma alanine aminotransferase (ALT), aspartate aminotransferase(AST) and hepatic lipid peroxidation (LP) levels and improved the restraint stress-induced decrease in hepatic glutathione (GSH), and glycogen levels, thus showing the significant antistress potential of the test drug.

Augmentation of immune response by chicoric acid through the modulation of CD28/CTLA-4 and Th1 pathway in chronically stressed mice

This study demonstrates the protective effect of chicoric acid (CA) on chronic restraint stress-induced altered T lymphocyte subset distribution and corresponding cytokine secretion patterns in experimental Swiss albino mice. CA has the potential to restore diminished immune response and Th1/Th2 homeostasis in chronically stressed mice as evident by significant increase in lymphocyte proliferation and CD3(+), CD4(+) and CD8(+) T cell population. Interestingly, chicoric acid imparted immunostimulation mainly by upregulating the expression of CD28 and CD80 and downregulating CTLA-4. It exerted stimulatory effect on IL-12, IFN-gamma and IL-2 and suppressed the increased IL-10 levels in chronically stressed mice. It also exhibited a significant lowering effect on raised corticosterone levels and reversed the chronic stress-induced hypertrophy of adrenal glands and atrophy of thymus and spleen, thereby showing its normalizing effect on HPA axis. Our results reveal that CA has the potential to reverse the impact of chronic restraint stress on immune status by normalizing corticosterone levels and augmenting Th1 cytokine profile along with the co-stimulatory molecules particularly CD28/CTLA-4 pathway that plays a very important role in generation of an effective immune response in immune compromised situations.

Immunosuppressive properties of Pluchea lanceolata leaves.

Objective: To investigate the immunosuppressive potential of Pluchea lanceolata 50% ethanolic extract (PL) and its bioactive chloroform fraction (PLC). Materials and Methods: Preliminary screening of the Pluchea lanceolata 50% ethanolic extract (PL) was carried out with basic models of immunomodulation, such as, the humoral antibody response (hemagglutination antibody titers), cell-mediated immune response (delayed-type hypersensitivity), skin allograft rejection test, in vitro (C. albicans method), and in vivo phagocytosis (carbon clearance test). The extract was then fractionated with chloroform, n-butanol, and water to receive the respective fractions by partitioning. These fractions were employed for flow cytometry to study the T-cell specific immunosuppressive potential of these fractions. Results: Oral administration of PL at doses of 50 to 800 mg/kg in mice, with sheep red blood cells (SRBC) as an antigen, inhibited both humoral and cell-mediated immune responses, as evidenced by the production of the circulating antibody titer and delayed-type hypersensitiviy reaction results, respectively, and the immune suppression was statistically significant (P < 0.01) in Balb/C mice. PL also decreased the process of phagocytosis both in vitro (31.23%) and ex vivo (32.81%) and delayed the graft rejection time (30.76%). To study the T-cell-specific activities, chloroform, n-butanol, and water fractions from P. lanceolata were tested for T-cell specific immunosuppressive evaluation, wherein only the chloroform fraction (PLC) showed significant (P < 0.01) suppression of CD8+ / CD4+ T-cell surface markers and intracellular Th1 (IL-2 and IFN-Y) cytokines at 25 – 200 mg/kg p.o. doses. PLC, however, did not show significant suppression of the Th2 (IL-4) cytokine. Conclusion: The findings from the present investigation reveal that P. lanceolata causes immunosuppression by inhibiting Th1 cytokines.

Amelioration of adjuvant induced arthritis by apocynin

The premise of the study was to investigate the antiarthritic potential of apocynin (APO) in Balb/c mice (in vivo). The experiment showed a dose‐dependent decrease in oedema and showed a suppression of proinflammatory cytokines such as TNF‐α and IL‐1β and mediators such as prostaglandin E2 (PGE2) and LTB4. At oral doses of 0.5, 1.0, 2.0 and 4.0 mg/kg once daily during the course of the experiment, APO induced an inhibition of T cell mediated immune response causing suppression of CD4+ and CD8+ T cells and of intracellular interferon‐gamma (IFN‐γ) by flow cytometry in arthritic mice. In parallel there was a dose‐dependent inhibition in vascular permeability causing an inhibition in the migration of leucocytes and exudate volume at the site of the inflammatory reaction. These observations validate the immunoregulatory potential of apocynin. Copyright

Downregulation of pro‐inflammatory cytokines by lupeol measured using cytometric bead array immunoassay

The objective of the study was to investigate the activity of Lupeol (LUP) on proinflammatory and anti‐inflammatory cytokines in the pleural exudate from male swiss albino mice. We applied Cytometric bead array technology for simultaneously measurement of these cytokines in pleurisy induced mice treated with lupeol in graded oral doses. Cytometric bead array uses the sensitivity of amplified fluorescence detection by flowcytometer to measure soluble analytes in a particle based immune assay. This assay can accurately quantitate 5 cytokines in a 50 microlitre sample volume. Oral administration of LUP at doses of 25, 50, 100 and 200 mg/kg p.o. produced dose related inhibition of IL‐2, IFN‐gamma and TNF‐α in the pleural exudate with the most significant effect at 100 mg/kg oral dose. LUP had a non significant inhibitory effect on the levels of IL‐4 and IL‐5. Copyright

Alcoholic extract of Cicer microphyllum augments Th1 immune response in normal and chronically stressed Swiss albino mice

Objective  The purpose of this study was to observe the effect of an alcoholic extract of Cicer microphyllum (I3M/38/A001) (whole plant without seeds and flowers) on the immunological parameters of sheep red blood cell immunized normal and chronically stressed Swiss albino mice.

Protective effect of Labisia pumila on stress-induced behavioral, biochemical, and immunological alterations.

The aim of the present study was to investigate the antistress potential of LABISIA PUMILA aqueous extract (LPPM/A003) using a battery of tests widely employed in different stressful situations. Pretreatment of experimental animals with LPPM/A003 caused an increase in the swimming endurance and hypoxia time and also showed the recovery of physical stress-induced depletion of neuromuscular coordination and scopolamine induced memory deficit. LPPM/A003 at graded doses reversed the chronic restraint stress (RST), induced depletion of CD4 (+) and CD8 (+) T lymphocytes, NK cell population, and corresponding cytokines expression besides downregulating the stress-induced increase in plasma corticosterone, a major stress hormone. In addition, LPPM/A003 reversed the chronic stress-induced increase in adrenal gland weight, serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and hepatic lipid peroxidation (LP) levels and augmented the RST induced decrease in hepatic glutathione (GSH), thymus and spleen weight. Thus, we conclude that LPPM/A003 has the ability to reverse the alterations produced by various stressful stimuli and therefore restores homeostasis.