Anpurna Kaul

Immunomodulating agents of plant origin. I: Preliminary screening

The immunobiological activity was investigated of certain medicinal plants widely used in the Ayurvedic and Unani systems of medicine for treatment of chronic infections and immunological disorders. The effect of an ethanolic extract of each drug was studied on delayed type hypersensitivity, humoral responses to sheep red blood cells, skin allograft rejection, and phagocytic activity of the reticuloendothelial system in mice. Picrorhiza kurroa was found to be a potent immunostimulant, stimulating both cell-mediated and humoral immunity. Tylophora indica, Aconitum heterophyllum and Holarrhena antidysenterica appeared to stimulate phagocytic function while inhibiting the humoral component of the immune system. Tinospora cordifolia and Ocimum gratissimum appeared to improve the phagocytic function without affecting the humoral or cell-mediated immune system. Hemidesmus indicus suppressed both the cell-mediated and humoral components of the immune system.

Immunomodulatory activity of Asparagus racemosus on systemic Th1/Th2 immunity: Implications for immunoadjuvant potential

ETHNOPHARMACOLOGICAL RELEVANCE Roots of Asparagus racemosus Willd (Shatavari in vernacular) are widely used in Ayurveda as Rasayana for immunostimulation, galactogogue as also in treatment of conditions like ulcers and cancer. Various studies have indicated immunomodulatory properties of Shatavari root extracts and formulations. AIM OF THE STUDY To study the effect of standardized Asparagus racemosus root aqueous extract (ARE) on systemic Th1/Th2 immunity of SRBC sensitized animals. MATERIALS AND METHODS We used HPTLC to quantify steroidal saponins (Shatavarin IV, Immunoside) and flow cytometry to study effects of ARE on Th1/Th2 immunity. SRBC specific antibody titres and DTH responses were also monitored as markers of Th2 and Th1 responses, respectively. We also studied lymphocyte proliferation. Cyclosporin, cyclophosphamide and levamisole were used as controls. RESULTS Treatment with ARE (100mg/(kg b.w.p.o.)) resulted in significant increase of CD3(+) and CD4/CD8(+) percentages suggesting its effect on T cell activation. ARE treated animals showed significant up-regulation of Th1 (IL-2, IFN-g) and Th2 (IL-4) cytokines suggesting its mixed Th1/Th2 adjuvant activity. Consistent to this, ARE also showed higher antibody titres and DTH responses. ARE, in combination with LPS, Con A or SRBC, produced a significant proliferation suggesting effect on activated lymphocytes. CONCLUSION The study suggests mixed Th1/Th2 activity of ARE supports its immunoadjuvant potential.

Immunomodulatory Activity of Boswellic Acids (Pentacyclic Triterpene Acids) fromBoswellia serrata

Boswellic acids, a mixture of pentacyclic triterpene acids (BA) obtained from Boswellia serrata Roxb., have been investigated for their effect on cell mediated and humoral components of the immune system and the immunotoxicological potential. A single oral administration of BA (50–200 mg/kg) inhibited the expression of the 24 h delayed type hypersensitivity (DTH) reaction and primary humoral response to SRBC in mice. The secondary response was appreciably enhanced at lower doses. In a multiple oral dose schedule BA (25, 50 and 100 mg/kg) reduced the development of the 24 h DTH reaction and complement fixing antibody titres and slightly enhanced the humoral antibody synthesis. In concentrations greater than 3.9 μg/mL BA produced almost similar and dose related inhibition of proliferative responsiveness of splenocytes to mitogens and alloantigen. Preincubation of macrophages with different concentrations of BA enhanced the phagocytic function of adherent macrophages. Prolonged oral administration of BA (25–100 mg/kg/d×21 days) increased the body weight, total leukocyte counts and humoral antibody titres in rats. It is not cytotoxic nor does it cause immunosuppression.

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.

Immunopharmacological properties of azepino [2, 1-b] quinazolin-12(6H)-one-7, 8, 9, 10-tetrahydro (RLX)

The effect of azepino [2,1-b]quinazolin-12(6H)-one-7, 8, 9, 10-tetrahydro (RLX) was studied on cell-mediated and humoral components of the immune system. In single (50, 100 and 200 mg/kg) and multiple (6.25, 12.50, 25 and 50 m/kg) oral dose schedules RLX significantly reduced the early (4 h) and delayed (24 and 48 h) hypersensitivity reactions to SRBC in mice. Daily oral administration of RLX (25, 50 and 100 mg/kg) produced a dose-related reduction in developing adjuvant arthritis in rats. In carrageenan-induced pleurisy in rats RLX (25, 50 and 100 mg/kg p.o.) caused a marked reduction in the volume of pleural exudate (25.26-59.64%) and infiltration of leucocytes (28.75-50.29%) into the pleural cavity. RLX produced marked inhibition of humoral antibody synthesis both in mice and rats and that of complement fixing antibody in mice. It was not cytotoxic and showed no appreciable effect on the responsiveness of splenocytes to mitogens. The observed effect of RLX on cell-mediated and humoral immune responses does not appear to be the result of general toxicity.

Immunostimulatory activity of plumieride an iridoid in augmenting immune system by targeting Th-1 pathway in balb/c mice

Abstract Plumieride, an iridoid glucoside isolated from Plumieria acutifolia leaves was investigated for its immunostimulatory activity on humoral, cell mediated and intracellular cytokine levels in sensitized and unsensitised balb/c mice. Plumieride restores the suppressed cell mediated, humoral immune response and also enhances the release of TNF‐ &agr;, IFN‐&ggr;, and IL‐2 (Th‐1) in immune compromised cyclosporine and cyclophosphamide treated balb/c mice. It does not stimulate the IL‐4 (Th‐2) expression. Plumieride demonstrates significant augmentation of Th‐1 response in immunosuppressed balb/c mice. Results of the present study suggested that plumieride can be developed as an immunostimulatory adjuvant to treat the immune suppression in various disease condition(s). Graphical abstract Figure. No caption available. HighlightsPlumieride, an iridoid stimulated the immune system in immune suppressed Balb/c mice.Plumieride stimulated the T cells by increasing the expression of TNF‐ &agr;, IFN‐&ggr;, and IL‐2.Plumieride stimulated the immune system by Th‐1 pathway.

Antioxidant and Immunomodulatory Potential of Cobra lily Species of North-western Himalayan Region: A Comparative Analysis

Abstract This study explored the antioxidant and immunomodulatory potential of two ethno-medicinally valuable species belonging to genus Arisaema viz., Arisaema flavum and Arisaema propinquum. The arial parts and tubers of these species were subjected to polarity based extraction using different solvents. In vitro antioxidant studies were performed in terms of DPPH radical scavenging, chelation power on ferrous ions, reducing power and FRAP assays. Immunomodulatory studies were also determined by evaluating Humoral antibody response (Hab) and Delayed type hypersensitivity response (DTH). The results depicted that A. flavum exhibited relatively better antioxidant and immunomodulatory potential than A. propinquum. Methanol extract of A. flavum leaves demonstrated promising antioxidant activity with DPPH radical scavenging IC value of 0.406±0.43 mg/ml (R2 = 0.9643), FRAP value of 2176 mM of Fe2+/mg extract (R2 = 0.9962) and reducing power with EC 1.25±0.27mg/ml (R2 = 0.9948) than the extracts of A.propinquum. Chelation capacity of methanol extracts of A. flavum (55 %) leaves was found to be quite significant as compared to that of A. propinquum (51 %) at 100 µg/ml concentration. A. flavum leaf methanol extract was also found have immune enhancing effect by increasing the humoral response by 83 % and DTH response by 100 % in immune suppressed mice. The present work concludes that the antioxidative power of A. flavum surpasses that of A. propinquum whereas in case of immunomodulation, A. flavum has considerable enhancing effect on humoral response and A. propinquum demonstrated better DTH response.