Search

In the present study we have evaluated the immunopotentiating activity of Rhodiola aqueous extract (RAE) in rats. The efficacy of RAE was determined by using strong antigen tetanus toxoid (TT) and weak antigen Ovalbumin (OVA). The dynamic changes in humoral and cell-mediated immune response were measured. The results indicated that the TT specific immunoglobulin levels were significantly enhanced by RAE and were at par with complete Freund’s adjuvant (CFA). The level of OVA induced antibody response was also enhanced by RAE. It was observed that TT and OVA in combination with CFA or RAE could evoke a significant delayed type hypersensitivity (DTH) response, confirming its potential to generate strong cell-mediated immunity (CMI). The anti-inflammatory or immunosuppressive effect of RAE was evaluated in adjuvant-induced arthritis model (AIA). RAE could not suppress the swelling response. Therefore, this study suggests that RAE has adjuvant/immunopotentiating activity in terms of humoral as well as cell-med...

There are several reports, which suggest that the consumption of foods rich in flavonoids is associated with a lower incidence of certain degenerative diseases, including cardiovascular disease. Flavones, of Seabuckthorn (SBT) (Hippophae rhamnoides L.) fruit berry can modulate the production and level of several signaling molecules associated with immune function and inflammation in vitro, including several cytokines. We have evaluated the immunomodulatory activity of ethanolic solution of SBT flavone (FLV) in human peripheral blood mononuclear cells (PBMCs). The SBT flavone was found to stimulate production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in PBMCs. However, increased expressions of p-IkappaB, NF-kappaB, and p-p38 were found in flavone-treated human PBMCs with significantly suppressed expression of CD25 (IL-2R). There was no alteration found in the nitric oxide (NO) production in mouse macrophage cell line RAW 264.7. These observations suggest that stimulation of IL-6 and TNF-alpha secretion may contribute to the putative beneficial effects of dietary flavone against microbial infection.

High throughput screening is commonly defined as automatic testing of potential drug candidates at a rate in excess of 10,000 compounds per week. The aim of high throughput drug discovery is to test large compound collections for potentially active compounds ('hits') in order to allow further development of compounds for pre-clinical testing ('leads'). High throughput technology has emerged over the last few years as an important tool for drug discovery and lead optimisation. In this approach, the molecular diversity and range of biological properties displayed by secondary metabolites constitutes a challenge to combinatorial strategies for natural products synthesis and derivatization. This article reviews the approach of High throughput technique for the screening of natural products for drug discovery.

Objective To study protein–protein interaction between heterogeneous nuclear ribonucleoprotein H (hnRNP H) and Dengue virus (DENV) proteins. Methods DENV proteins were screened against the host hnRNP H protein, in order to identify the host-viral protein–protein interactions in DENV infected THP-1 cells by co-immunoprecipitation. The co-localization of the interacting proteins was further confirmed by immunofluorescence microscopy. Results The host protein hnRNP H was found to interact with DENV non-structural 1 protein and help the virus to multiply in the cell. Conclusions The non-structural 1 glycoprotein is a key modulator of host immune response and is also involved in viral replication. Therefore, disruption of this key interaction between hnRNP H and DENV non-structural 1 could be an important therapeutic strategy for management of DENV infection.

High altitude hypoxia is known to induce an inflammatory response in immune cells. Hypoxia induced inflammatory chemokines may contribute to the development of high altitude pulmonary edema (HAPE) by causing damage to the lung endothelial cells and thereby capillary leakage. In the present study, we were interested to know whether chronic inflammation may contribute to HAPE susceptibility. We examined the serum levels of macrophage inflammatory protein-1α (MIP-1α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 in group (1) HAPE Susceptible subjects (n = 20) who had past history of HAPE and group (2) Control (n = 18) consist of subjects who had stayed at high altitude for 2 years without any history of HAPE. The data obtained confirmed that circulating MCP-1, MIP-1α were significantly upregulated in HAPE-S individuals as compared to the controls suggestive of chronic inflammation. However, it is not certain whether chronic inflammation is cause or consequence of previous episode of HAPE. The moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence of enhanced level of inflammatory chemokines found in this study support the hypothesis that subjects with past history of HAPE have higher baseline chronic inflammation which may contribute to HAPE susceptibility.

Hippophae salicifolia (HS) and Hippophae rhamnoides turkestanica (HRT) are abundantly found species of Hippophae in Himalayan region of India. As these plants thrive under extreme climatic conditions, it is suspected that these plants must have a unique adaptogenic property against high-altitude stress. To keeping these views in our mind, the present study was planned to evaluate the mechanism of action of aqueous extract of HS and aqueous extract of HRT against multiple stress [cold-hypoxia-restraint (C-H-R)] for their adaptogenic activity. The present study reported the adaptogenic activity of HS in facilitating tolerance to multiple stress, CHR in rats. Pre-treatment with aqueous extract of HS significantly attenuated reactive oxygen species (ROS) production, protein oxidation, and lipid peroxidation and also showed role in maintaining antioxidant status as similar to control rats. Since protein oxidation was decreased by pre-treatment of HS, protein homeostasis was also sustained by regulation of heat shock proteins (HSP70 and HSP60). Interestingly, heme oxygenase-1 (HO-1), Vascular Endothelial Growth Factor (VEGF), and nitric oxide (NO) level was also increased in HS pre-treated rats depicted its adaptogenic activity against multiple stress, CHR. Conclusively, aqueous extract of HS could use an adaptogen for high altitude-associated multiple stress (CHR).

The Antarctic milieu comes with extreme cold, intense UV radiation, white-outs, varying magnetic fields, sleep deprivation, altered circadian biorhythms, memory loss, isolation,-causing significant physiological and psychological stresses. These conditions closely resemble space travel, with striking similarity in character of peculiar climate, remoteness, constrained living spaces, disturbed sleep cycles, and environmental stress. Due to its extreme weather conditions, and unique geo-location around the South Pole, it is one of the last frontiers for the human race. Thus the geographic isolation and prolonged stressful stay at Antarctica makes it interesting to study the body responses of expeditioners under extreme environmental conditions. Two teams participated in the study, in 28th Indian Scientific Expedition to Antarctica. The first team included members for short “summer” expedition, while the second team as “Winter team”, included members exposed for long term to Antarctic environment. The present study was performed to study the changes occurring in proteomic profile related to immune system. Blood samples were collected in chronological sequence, including i) baseline control ii) during ship journey and iii) at Maitri (Antarctica), during the months of March, May, August and November. The sera samples collected were subjected to differential expression of protein analysis by 2D Gel electrophoresis followed by MALDI-TOF analysis. Catecholamine was also estimated as a measure of stress. Results of 2D gel and MALDI-TOF-TOF analysis revealed significantly increased level of Complement Factor 3 during ship journey and during peak winter in August. Further detailed analysis of complement pathway by ELISA revealed activation of complement system during the acute and chronic stress of Antarctica.

Domain II of Mycobacterium tuberculosis (Mtb) heat shock protein 70 (HSP70), spanning amino acid residues 161-370, was covalently linked to a recently described synthetic dengue virus antigen to study the influence of the former on the immunogenicity of the latter. Using an enzyme-linked immunosorbent assay, dengue antigen-specific antibody titers elicited by the fusion protein in Balb/c mice were an order of magnitude higher than those elicited by either the synthetic dengue antigen alone or a physical mixture of the dengue antigen plus Mtb HSP70 domain II protein. Our data demonstrate that (i) Mtb HSP70 domain II is capable of potentiating B-cell response and (ii) it should be covalently linked to the target antigen to do so.

Immunomodulatory activity of Seabuckthorn (SBT) leaf extract was evaluated in adjuvant induced arthritis (AIA) rat model. Inflammation was induced by injecting Complete Freund's Adjuvant (CFA) in the right hind paw of rats. SBT extract was administered intraperitoneally to treat the inflammation. The extent of inflammation and treatment response was evaluated by clinical analysis, scintigraphic visualization using technitium-99m-glutathione (Tc99m-GSH) and lymphocyte proliferation. Serial evaluation was carried out on days 1, 7, 14, 21 and 28 after creation of inflammation. The Tc99m-GSH uptake in the inflamed leg was compared with the normal contralateral leg of the same animal. The measurements were done by obtaining scintigraphic images using gamma camera and an online computer. Both qualitative and quantitative evaluation of radiotracer accumulation was considered to evaluate the anti-inflammatory response. The lymphocyte proliferation study revealed cellular immunosuppression during the early phase of the disease. Administration of SBT extract on the same day or 5 days prior to inflammatory insult into the joint, significantly reduced the inflammation as compared to the untreated animals in a dose dependent manner. These observations suggest that the SBT leaf extract has a significant anti-inflammatory activity and has the potential for the treatment of arthritis.

Over the last decade, extensive research for development of new vaccine adjuvants is being carried out. Present generation vaccines, particularly those based on recombinant proteins and DNA, are not only less reactogenic and also less immunogenic. Therefore, there is an urgent need for the development of new and improved vaccine adjuvants. Many novel adjuvants have been cleared for license, and many are in late stages of clinical trials. Recent investigations in innate immunity have offered new insights into immunostimulatory actions of adjuvants and have facilitated a more rational selection of adjuvants. Despite the impressive response of approved adjuvants in generating immunity against pathogens, there remains a need for improved adjuvants that enhance strong T-cell immunity and protective antibody response. The discovery of more potent adjuvants will also allow engineering of vaccines against infections that do not naturally elicit protective immunity. A logical approach to the development of new and more effective vaccine adjuvants requires a better understanding of the action of adjuvant-antigen formulations. Here, we discuss these advances and the need for better adjuvant development.

The Antarctic context is an analogue of space travel, with close similarity in ambience of extreme climate, isolation, constrained living spaces, disrupted sleep cycles, and environmental stress. The present study examined the impact of the harsh habitat of Antarctica on human physiology and its metabolic pathways, by analyzing human serum samples, using 1 H‐NMR spectroscopy for identification of metabolites; and quantifying other physiological and clinical parameters for correlation between expression data and metabolite data. Sera from seven adult males (of median age 36 years) who participated in this study, from the 28th Indian Expeditionary group to the Antarctica station Maitri, were collected in chronological sequence. These included: i) baseline control; ii) during ship journey; iii) at Antarctica, in the months of March, May, August and November; to enable study of temporal evolution of monitored physiological states. 29 metabolites in serum were identified from the 400 MHz 1 H‐NMR spectra. Out of these, 19 metabolites showed significant variations in levels, during the ship journey and the stay at Maitri, compared to the base-line levels. Further biochemical analysis also supported these results, indicating that the ship journey, and the long-term Antarctic exposure, affected kidney and liver functioning. Our metabolite data highlights for the first time the effect of environmental stress on the patho-physiology of the human system. Multivariate analysis tools were employed for this metabonomics study, using 1 H‐NMR spectroscopy.

Padhy, Gayatri, Niroj Kumar Sethy, Lilly Ganju, and Kalpana Bhargava. Abundance of plasma antioxidant proteins confers tolerance to acute hypobaric hypoxia exposure. High Alt Med Biol 14:289–297, 2013—Systematic identification of molecular signatures for hypobaric hypoxia can aid in better understanding of human adaptation to high altitude. In an attempt to identify proteins promoting hypoxia tolerance during acute exposure to high altitude, we screened and identified hypoxia tolerant and susceptible rats based on hyperventilation time to a simulated altitude of 32,000 ft (9754 m). The hypoxia tolerance was further validated by estimating 8-isoprotane levels and protein carbonyls, which revealed that hypoxia tolerant rats possessed significant lower plasma levels as compared to susceptible rats. We used a comparative plasma proteome profiling approach using 2-dimensional gel electrophoresis (2-DGE) combined with MALDI TOF/TOF for both groups, along with an hypoxic control group. This resulted in the identification of 19 differentially expressed proteins. Seven proteins (TTR, GPx-3, PON1, Rab-3D, CLC11, CRP, and Hp) were upregulated in hypoxia tolerant rats, while apolipoprotein A-I (APOA1) was upregulated in hypoxia susceptible rats. We further confirmed the consistent higher expression levels of three antioxidant proteins (PON1, TTR, and GPx-3) in hypoxia-tolerant animals using ELISA and immunoblotting. Collectively, these proteomics-based results highlight the role of antioxidant enzymes in conferring hypoxia tolerance during acute hypobaric hypoxia. The expression of these antioxidant enzymes could be used as putative biomarkers for screening altitude adaptation as well as aiding in better management of altered oxygen pathophysiologies.

Hypoxia is a condition of low pO2, which creates a unique microenvironment affecting cell phenotype and subsequent immune response generation. Little is known about the impact of hypoxia on the phenotypic expression of NK cell, TREM-1, TLR-4 and inflammatory chemokines. In the present study we have determined the frequency of peripheral blood populations of CD16/CD56 (NK Cells) expressing cells, presence of activation marker CD354 (TREM-1), Toll like receptor (CD 284) on the cell surface and chemokines IL-8 and RANTES in the cellular supernatant of normoxia and hypoxia exposed cells by flow cytometry. GRP-78 expression was determined by reverse transcriptase polymerase chain reaction. The blood was collected from healthy individuals and exposed to normoxic and hypoxic (0.5 %) environment for 24 h. The percentage of NK cells (CD 16/56) was marginally up regulated while TLR-4 expression was diminished in hypoxia exposed cells as compare to the normoxic cells. TREM-1 expression was significantly up-regulated (p

Plant Derived Antivirals:A Potential Source of Drug Development Plants have been the traditional source of active substances for most therapies. Plant derived natural compounds have received increasing attention for their antiviral potential. Typical example is constituents of Sarracenia purpurea which is found active particularly against Herpes Simplex Virus (HSV).

Environmental stress at high altitude affects the myocardium at the physiological and molecular level. Characterized by hypobaric hypoxia and low temperatures, the cumulative impact of these stressors on the protein folding homeostasis in the heart is yet unexplored. The present study evaluates the collective effect of cold and hypoxia on the myocardial protein oxidation and activation of the endoplasmic reticulum (ER) stress response. Adult rats were exposed to either a singular acute stress of cold (10 °C; C), hypobaric hypoxia (7620 m; H) or simultaneously to both cold and hypobaric hypoxia (CH) for 6 h. Hypoxic stress amplified the free radical generation in H and CH groups, leading to enhanced HIF-1α expression. Coupled to cold stress, reduced oxygen availability caused substantial protein oxidative modifications, as well as cardiac tissue injury and matrix remodeling, evident in the histological staining. Presence of oxidized proteins caused a significant upregulation in expression of ER chaperones GRP78 and PDI in the cold hypoxia exposed animals. Enhanced proteolytic activity signaled the removal of misfolded proteins. Linked intricately to cellular stress response, cell survival kinases were expressed higher in CH group; however apoptotic CHOP (C/EBP homologous protein) expression remained unaltered. Administration of ER stress inducer, tunicamycin along with cold hypoxic stress, caused a discernible increase in protein oxidation and GRP78 expression, along with a significant elevation in proteasome and apoptotic activity. Highlighting the significance of a synergistic, rather than individual, effect of low oxygen and temperature on the protein folding machinery, our study provides evidence for the activation of ER stress response in the myocardium under acute high altitude stress.

The Antarctic continent on the planet Earth is full of environmental extremes. It is considered as natural stress model. Therefore, the present study examined the effect of harsh environment on the certain salivary markers of 28th Indian Antarctic expeditioners. Thirty healthy men and women (median age 36 year; range 22–61 year) participated in this study. Parameters measured were salivary IgA (SIgA), IgM (SIgM), TGF-β and cortisol level at three different time points: (I) before leaving India on 26th October 2008 for base line level; (II) after 1 month on-board journey on 31st January 2009 in Southern Ocean and (III) after 1 month staying at Maitri, Antarctica on 3rd March 2009. Our observation indicated that Ship borne journey and Antarctic environment increased the SIgA levels while that of SIgM level was not altered on-board but decreased by staying for 1 month at Antarctica. No significant alteration was found in the TGF-β and cortisol level at any point of time. The present study concluded that ship borne journey and Antarctic environment may induce the SIgA level while SIgM level decreased in environmental extremes of Antarctica.

The Antarctic continent is full of environmental extremes like isolation, cold, UV exposure, and blizzards etc. The present study was conducted to analyze the effect of ship borne journey and the impact of Antarctic harsh environment on serum immunoglobulin (IgG, IgM, IgA) levels and their relationship with seasickness in Indian expeditioners. It was observed that one month onboard ship journey induced an increase in serum IgA levels and decrease in IgG levels while after being one month off board at the Indian research station Maitri, decreased levels of IgG and increased levels of IgA were found. IgM levels were not altered in comparison to the base line control. Moreover, serum IgG level showed a positive correlation while IgA level showed a negative correlation with seasickness. The stimulation of human peripheral blood mononuclear cells (PBMCs) with serum of expeditioner at different places showed that IgA at lower dose induces the release of pro-inflammatory IL-1β, and IL-6 cytokines from PBMCs while higher dose of IgA decreases proinflammatory cytokine production. The release of anti-inflammatory cytokines TGF-β1 and IL-10 was not significantly altered. Thus, the present study concluded that ship borne journey and Antarctic environment lead to increased serum IgA levels while decreased IgG levels. It also suggests that serum IgA level could be a possible biomarker for environmental stress.

The pathogenic mechanism of dengue virus infection is related to the host responses within target cells, and therefore we assessed intracellular changes in stress proteins following dengue virus infection. This study provides evidence that Hsp70 helps in viral multiplication by suppressing the type 1 interferon response. Dengue virus infection in human monocytic THP-1 cells led to overexpression of Hsp70, which also acts as a chaperone. The functional role of Hsp70 in dengue virus multiplication was identified by downregulating the Hsp70 gene with its specific siRNA duplexes, which led to a decrease in viral RNA copy numbers in cellular supernatants and intracellular viral load. It also resulted in an increased IFN-α level, which mediates its antiviral effect through double-stranded RNA-induced protein kinase-PKR. Collectively these results suggest that an increased level of Hsp70 expression in dengue-virus-infected THP-1 cells assists in viral replication by escaping the antiviral effect of type 1 interferon.

It has become apparent that extreme environmental conditions of Antarctic continent alters many immune responses. The present study was conducted on 28th Indian Antarctic expeditioners. The investigations were carried out to explore the effect of multiple stresses like isolation, cold and UV exposure on human immunity. Thirty blood samples were collected between 6 and 7 AM, after an overnight fast at different stages of the expedition - viz. the pre-exposure sample was collected at Delhi on 25(th) October 2008. The expedition started its ship journey from Capetown, on 6(th) January, 2009 and on-board blood was collected on 31(st) January 2009. After 1 month stay at Maitri, blood was collected on 3(rd) March 2009. Different parameters studied included levels of cytokines, chemokines and cortisol. The ship-borne journey induced a dramatic increase in TNF-α, IFN-γ, and B cell activating factor (BAFF) levels and moderate decreases in TGF-β and cortisol levels. However, after being off board for 1 month at Maitri station, levels of above cytokines, cortisol and BAFF were decreased but MIP-1α was significantly increased. These data for the first time suggest that ship-borne journey to the Antarctic continent results in tremendous stress to the body, which eventually resulted in increased TH1-biased immunity.

High altitude may be defined as elevations as low as 1500 meters to those as high as 8800 meters. Very few studies have been conducted so far at high altitude for the specific purpose of monitoring different immune parameters in humans. Military personnel and mountaineers may be required to perform in environmental extremes such as high altitude. The stressors they experience are numerous and varied, e.g., high altitude, humidity and the availability of food and water, prolonged moderate to heavy physical activities, limited or inadequate sleep, increased susceptibility to infection and injury, etc. In this article we review the immunological consequences of high altitude exposure.

In the present study we have evaluated the immunopotentiating activity of Rhodiola aqueous extract (RAE) in rats. The efficacy of RAE was determined by using strong antigen tetanus toxoid (TT) and weak antigen Ovalbumin (OVA). The dynamic changes in humoral and cell-mediated immune response were measured. The results indicated that the TT specific immunoglobulin levels were significantly enhanced by RAE and were at par with complete Freund's adjuvant (CFA). The level of OVA induced antibody response was also enhanced by RAE. It was observed that TT and OVA in combination with CFA or RAE could evoke a significant delayed type hypersensitivity (DTH) response, confirming its potential to generate strong cell-mediated immunity (CMI). The anti-inflammatory or immunosuppressive effect of RAE was evaluated in adjuvant-induced arthritis model (AIA). RAE could not suppress the swelling response. Therefore, this study suggests that RAE has adjuvant/immunopotentiating activity in terms of humoral as well as cell-mediated immune response against strong antigen like TT and weak antigen like OVA.

Antigens of Mycobacterium w, a saprophytic fast growing organism having antigenic epitopes cross-reactive with Mycobacterium leprae and Mycobacterium tuberculosis, were coated on to latex beads (0.33 micron Zn size), and the reactivity tested with sera of tuberculosis and Hansen's disease (HD) patients. Seventy nine percent of lepromatous leprosy (LL) and eighty five percent of pulmonary tuberculosis (TB) patients sera showed an agglutination reaction easily read by naked eye. Specificity of the test was further checked by testing sera of non-mycobacterial infection cases and all of them were found negative. Among apparently healthy controls, 4.3% were found positive from non-endemic and 8.8% from endemic area. The sensitivity of the assay is further enhanced from 78.7% to 90.4% and 85.7% to 91.6% in both LL HD and pulmonary tuberculosis respectively, by using immune complexes extracted from the patients sera. Potential of these antigen coated beads to detect the two major human mycobacterial disease, LL HD and pulmonary TB was also put evidence in a double blind study on coded sera samples obtained from various hospitals in India. The antigen coated beads are stable for upto 6 months at 4 degrees C. The latex slide agglutination test reported here, is simple, rapid, easy to perform and can be used even in rural areas of developing countries.

Rhodiola imbricata is a medicinal plant, native to mountainous regions of Asia, parts of Europe, and the Arctic. Traditionally it is recommended to help combat fatigue and restore energy. It exhibits anti-stress, anti-cancer, and immunostimulatory activities. However, the effect of Rhodiola on immunological responses largely remains unknown. In this study, we have investigated the effect of aqueous extract of R. imbricata rhizome (RAE), on Toll-like receptor-4 (TLR-4) and intracellular granzyme-B expression in mouse splenocytes. Furthermore, TH1/TH2 cytokine profile was analyzed in RAE-treated human peripheral blood mononuclear cells (PBMCs) using multiplex flowcytomix kit. Our findings suggest that RAE induces TLR-4 expression and intracellular granzyme-B in treated splenocytes while RAE stimulated IL-1 β , IL-6, and TNF- α in human PBMCs. The present study suggests that RAE stimulates the innate immune pathway and has potent immunostimulatory activity, which can be used in modulating the immune system of immunocompromised individuals.

Rhodiola imbricata is a medicinal plant having immunostimulating properties. The anti-proliferative effects of Rhodiola aqueous extract (RAE), were studied in human erythroleukemic cell line K-562 using MTT cell proliferation assay. The proliferation of K-562 was significantly decreased after 72h incubation with RAE at 100 and 200microg/ml. However, almost no suppressive effects could be detected in normal human peripheral blood lymphocytes or mouse macrophage cell line RAW-264.7. RAE was also found to induce intracellular reactive oxygen species (ROS) in K-562 cells at 200microg/ml when incubated overnight. The increased ROS generation may cause apoptosis, which was observed in AnnexinV-FITC and propidium iodide (PI) staining of cells treated with RAE for 72h in K-562 cells. Moreover, RAE arrested cell cycle progression in G2/M phase in early and late period of exposure. The anti-cancer activity of RAE was also confirmed by increased NK cell cytotoxicity. These observations suggest that aqueous extract of R. imbricata rhizome has very potent anti-cancer activities, which might be useful in leukemia cancer treatment.

Modulation of immune response to alleviate diseases has long since been of interest. Plant extracts have been widely investigated for their possible immunomodulatory properties. We have evaluated the immunomodulatory activity of aqueous extract of Rhodiola rhizome in human peripheral blood mononuclear cells (PBMCs) and mouse macrophage cell line RAW 264.7. The Rhodiola extract was found to stimulate production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in human PBMCs as well as RAW 264.7 cell line. It also increased production of nitric oxide synergistically in combination with lipopolysaccharide (LPS) in RAW 264.7. Rhodiola at 250 microg/ml increased the p-IkappaB expression in human PBMCs. Aqueous extract of Rhodiola (250 microg/ml) also activated the nuclear translocation of NF-kappaB in human PBMCs, which is comparable to the positive stimulant LPS. Thus, our present study suggests that Rhodiola most likely activates proinflammatory mediators via phosphorylated inhibitory kB and transcription factor NF-kB. Our study demonstrates immunostimulatory potential of aqueous extract of Rhodiola rhizome, that can be used for upregulation of immune response in patients with inadequate functioning of the immune system.

Nitric oxide (NO) is synthesized in large quantities by activated inflammatory cells and has been demonstrated to be involved in the pathogenesis of acute and chronic inflammatory conditions. Seabuckthorn (SBT) has been used in traditional medicine systems for the treatment of various diseases like cardiovascular, pain relief, oral inflammation and promotion of tissue regeneration. The present study focuses on the effects of SBT leaf extract on NO production induced by lipopolysaccharide (LPS) in the murine macrophage cell line RAW 264.7. In addition, cell viability, free radical-scavenging activity and inducible nitric oxide synthase (iNOS) expression were also evaluated. Seabuckthorn leaf extract significantly inhibited the enhanced production of NO induced by LPS in a dose dependent manner. Treatment with SBT did not reduce cell viability at any dose used. The extract showed significant scavenging of NO radicals released by the NO donor. Treatment of macrophages with SBT leaf extract also caused a significant inhibition of iNOS activation. These observations suggest that the inhibition of net NO production by SBT leaf extract may be due to its scavenging activity and/or its inhibitory effects on iNOS activation. The study suggests that SBT leaf extract has significant anti-inflammatory activity and has potential for the treatment of inflammatory diseases.

The immunomodulatory properties of amla (Emblica officinalis) and shankhpushpi (Evolvulus alsinoides) were evaluated in adjuvant induced arthritic (AIA) rat model. Injecting Complete Freund's Adjuvant (CFA) in right hind paw of the animals induced inflammation. The crude extracts of both the herbs were administered intraperitonially following a repeated treatment profile. The anti-inflammatory response of both the extracts was determined by lymphocyte proliferation activity and histopathological severity of synovial hyperplasia. Both the extracts showed a marked reduction in inflammation and edema. At cellular level immunosuppression occurred during the early phase of the disease. There was mild synovial hyperplasia and infiltration of few mononuclear cells in amla or shankhpushpi treated animals. The induction of nitric oxide synthase (NOS) was significantly decreased in treated animals as compared to controls. These observations suggest that both the herbal extracts caused immunosuppression in AIA rats, indicating that they may provide an alternative approach to the treatment of arthritis.

Purpose: Extensive studies in the last decade have shown that ER stress and cardiovascular pathophysiology are intimately intertwined. Recent evidence sheds light on the role of protein homoeostasis in the high altitude related disorders including pulmonary hypertension. Although individuals vary in their ability to cope with the harsh environmental conditions, oxidative modifications to the myocardial proteins, may contribute significantly to the hypoxic vulnerability. Assessing the hitherto unexplored significance of proteostasis in the differential response to hypoxic stress forms the crux of the present study. The study evaluates the potential of ER stress modulators as therapeutic agents in enhancing hypoxic tolerance. Methods: Sprague Dawley rats were exposed to simulated hypoxia equivalent to 223 mm Hg pressure, screened on the basis of gasping time and categorized as susceptible ( 25 min). Animals were administered either ER stress inducer tunicamycin (0.3mg/kg BW) or chemical chaperone, 4-phenylbutyric acid (200mg/kg BW) to assess the role of protein folding homeostasis. Biochemical assays were performed to identify protein modifications, proteolytic and apoptotic activities in the myocardial tissue extracts. Immunoblotting, immunohistochemistry and ELISA based expression analysis was done to elucidate expression of ER stress markers in the heart tissue. Results: Animals administered Tm showed a significant decrease in gasping time, along with greater protein oxidation and expression of UPR markers, including GRP78 and PERK highlighting the role of ER stress activation in enhancing hypoxic susceptibility. Conversely, 4-PBA significantly elevated the hypoxic tolerance as evident by the increase in gasping time and reduced levels of oxidative protein modifications. There was an appreciable increase in heat shock protein expression, as well as enhanced nitric oxide synthesis. This may be mediated in part by the induction of pro-survival signalling cascade including PI3K/Akt/mTOR/S6Kinase pathway and inhibition of apoptosis. Conclusion: 4-PBA thus increases stress tolerance through the attenuation of hypoxia induced protein misfolding. With recent research suggesting the occurrence of ER stress in high altitude related disorders like pulmonary hypertension, administration of chemical chaperones may form a novel therapeutic agent in increasing tolerance to environmental stress.