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Biomedical subjects

R C Sawhney

Publications and source records attributed to R C Sawhney.

At least 19 recordsLinked to original sources

Adaptogenic and safety evaluation of seabuckthorn (Hippophae rhamnoides) leaf extract: a dose dependent study.

The effects of seabuckthorn (Hippophae rhamnoides L., Elaeagnaceae), leaf aqueous extract were examined in rats for its adaptogenic activity and toxicity. Dose dependent adaptogenic study of extract was carried out at different doses administered orally, 30min prior to cold (5 degrees C)-hypoxia (428mmHg)-restraint (C-H-R) exposure. After sub-acute toxicity studies on 10 and 20 times doses of maximal effective dose administered for 14 days (single oral dose of 1g/kg and 2g/kg once daily) and maximal effective dose administered for 30 days (single oral dose of 100mg/kg once daily), biochemical and hematological parameters were studied in the serum and blood. The maximal effective adaptogenic dose of the extract was 100mg/kg body weight. No significant changes were observed in organ weight/body weight ratios, of any vital organ studied (except liver and kidney in 1g/kg and 2g/kg body weight doses, respectively), and biochemical and hematological parameters of the sub-acute drug treated animals in comparison to control rats. In acute toxicity study LD(50) of the extract was observed to be >10g/kg when given orally. These results indicate that seabuckthorn leaf aqueous extract possess potent adaptogenic activity with no toxicity even after sub-acute (30 days) maximal effective dose administration.

Animals↗

Studies on immunogenicity and protective efficacy of DnaJ of Salmonella Typhi against lethal infection by Salmonella Typhimurium in mice.

In the present study DnaJ (HSP40) of Salmonella enterica serovar Typhi has been evaluated for its immunogenicity and efficacy in protecting mice against lethal challenge by S. enterica serovar Typhimurium infection. DnaJ was amplified by PCR of the genomic DNA of S. Typhi and subsequently cloned in pQE-30 expression vector. The protein was induced by IPTG and purified using Ni-NTA chromatography under denaturing conditions. After refolding in vitro the immune response was evaluated by injecting 40 microg DnaJ protein/mouse i.p. on 0th, 7th and 28th day. The results showed a significant increase in antibody titre and lymphocyte proliferation in animals immunised with DnaJ as compared to control. Further there was an appreciable increase in IL-2, IL-4, IFN-gamma production in lymphocytes isolated from immunised mice as compared to control. In this limited study, immunisation of mice with DnaJ was found to provide 70% protection against lethal challenge by S. Typhimurium indicating the possible use of DnaJ as vaccine candidate against typhoid.

Animals↗

Flavonoids protect U-937 macrophages against tert-butylhydroperoxide induced oxidative injury.

The study was carried out to determine the relative efficacies of polyphenolic flavonoids, quercetin, catechin and epicatechin against tert-BOOH induced oxidative stress in human macrophage, U-937 cell line. Exposure of the cells to tert-BOOH oxidative stress resulted in a significant increase in cytotoxicity and reactive oxygen species (ROS) generation. Further, a significant decrease in mitochondrial membrane potential and increase in lipid peroxidation and DNA damage was observed in cells exposed to tert-BOOH. Pretreatment of cells with quercetin, catechin and epicatechin significantly inhibited tert-BOOH induced cytotoxicity by inhibiting ROS generation. The flavonoids inhibited DNA damage induced by tert-BOOH and preserved the mitochondrial transmembrane potential significantly. Epicatechin and catechin were found to be more efficient than quercetin in inhibiting tert-BOOH induced cellular damage.

Antioxidants↗

Aqueous extract of Rhodiola imbricata rhizome stimulates proinflammatory mediators via phosphorylated IkappaB and transcription factor nuclear factor-kappaB.

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.

Active Transport, Cell Nucleus↗

Protective effect of ethanolic and water extracts of sea buckthorn (Hippophae rhamnoides L.) against the toxic effects of mustard gas.

Ethanolic extract of H. rhamnoides L. leaf (HL-EOH), water and ethanolic extract of H. rhamnoides fruit (HF-W and HF-EOH), and H. rhamnoides flavone from fruit (HR-flavone) were evaluated against percutaneously administered sulphur mustard (SM), a chemical warfare agent. The animals administered with SM (9.7, 19.3 and 38.7 mg/kg) died at various days depending upon the dose and there was a significant reduction in the body weight. The H. rhamnoides extracts (1 g/kg; 3 doses; po) significantly protected the lethality, with a protective index of 2.4, 1.7, 1.7 and 2.2 for HL-EOH, HF-W, HF-EOH and HR-flavone respectively. Reduced glutathione (GSH) and oxidized glutalthione (GSSG) levels were reduced, and malondialdehyde (MDA) was elevated after percutaneous administration of SM. Oral administration of HL-EOH and HR-flavone significantly protected the body weight loss. Recovery in the levels of GSH, GSSG and MDA were also observed following oral administration of HL-EOH and HR-flavone. All the extracts were non-toxic and the LD50 was more than 5 g/kg. The present study shows that percutaneous administration of SM induces oxidative stress and ethanolic extract of leaf of H. rhamnoides and H. rhamnoides flavone from fruit can significantly protect it.

Animals↗

Immunomodulatory effects of seabuckthorn (Hippophae rhamnoides L.) against chromium (VI) induced immunosuppression.

The present study reports the immunomodulatory effects of seabuckthorn (Hippophae rhamnoides L.) leaf extract on cellular and humoral immune response by studying delayed-type hypersensitivity response, IL-2, IL-4 and gamma-IFN levels and antibody titres in chromium-induced immunosuppressed animals. Oral feeding of chromium (30 mg/kg bw) significantly inhibited antibody production and S-RBC induced delayed-type hypersensitivity response. Administration of leaf extract (100 mg/kg bw) along with chromium significantly inhibited chromium-induced immunosuppression. To understand the immunomodulatory mechanism of leaf extract, in vitro studies were carried out using rat lymphocytes. Addition of chromium resulted in a significant decrease in lymphocyte size and increased ROS generation. The leaf extract of seabuckthorn significantly inhibited chromium-induced reactive oxygen species (ROS) generation and maintained the cell size identical to that of control cells. Chromium treatment markedly inhibited the mitochondrial transmembrane potential by larger lymphocytes in particular, while the leaf extract restored the same significantly. Chromium also inhibited significantly concanavalin A (ConA) induced IL-2, IL-4 and gamma-IFN production in rat lymphocytes. The leaf extract (100 microg/ml) alone stimulated IL-2 and gamma-IFN production even in the absence of ConA and also inhibited chromium-induced decline in IL-2 and gamma-IFN production but it did not change IL-4 production. These observations suggest that the leaf extract of seabuckthorn has significant immunomodulatory activity and specifically activates the cell-mediated immune response.

Animals↗

Antioxidant activities of seabuckthorn (Hippophae rhamnoides) during hypoxia induced oxidative stress in glial cells.

The present study reports the cytoprotective and antioxidant properties of alcoholic leaf extract of seabuckthorn (SBT) against hypoxia induced oxidative stress in C-6 glioma cells. Exposure of cells to hypoxia for 12 h resulted in a significant increase in cytotoxicity and decrease in mitochondrial transmembrane potential compared to the controls. Further an appreciable increase in nitric oxide and reactive oxygen species (ROS) production was noted which in turn was responsible for fall in intracellular antioxidant levels and GSH/GSSG ratio. There was a significant increase in DNA damage during hypoxia as revealed by comet assay. Pretreatment of cells with alcoholic leaf extract of SBT at 200 mug/ml significantly inhibited cytotoxicity, ROS production and maintained antioxidant levels similar to that of control cells. Further, the leaf extract restored the mitochondrial integrity and prevented the DNA damage induced by hypoxia. These results indicate that the leaf extract of SBT has strong antioxidant and cytoprotective activity against hypoxia induced oxidative injury.

Antioxidants↗

Cytoprotective and antioxidant activity of Rhodiola imbricata against tert-butyl hydroperoxide induced oxidative injury in U-937 human macrophages.

The present study reports cytoprotective and antioxidant activity of aqueous and alcoholic extracts of Rhodiola imbricata rhizome on tert-butyl hydroperoxide (tert-BHP) induced cytotoxicity in U-937 human macrophages. There was an increase in cytotoxicity and apoptosis significantly in the presence of tert-BHP over control cells. The tert-BHP induced cytotoxicity can be attributed to enhanced reactive oxygen species (ROS) production which in turn is responsible for fall in reduced glutathione (GSH) levels; further there was a significant decrease in mitochondrial potential and increase in apoptosis and DNA fragmentation. Both aqueous and alcoholic extracts of Rhodiola rhizome at a concentration of 250 microg/ml were found to inhibit tert-BHP induced free radical production, apoptosis and to restore the anti-oxidant levels to that of the control cells. The alcoholic extract of Rhodiola showed higher cytoprotective activities than aqueous extract. These observations suggest that the alcoholic and aqueous extracts of Rhodiola have marked cytoprotective and antioxidant activities.

Antioxidants↗

Evaluation of antioxidant activity of leaf extract of Seabuckthorn (Hippophae rhamnoides L.) on chromium(VI) induced oxidative stress in albino rats.

The present study reports the antioxidant activity of Seabuckthorn (Hippophae rhamnoides), family Elaegnaceae, on chromium induced oxidative stress in male albino rats. Oxidative stress was induced in the rats by force-feeding of potassium dichromate equivalent to a dose of 30mg/kg body weight (BW) of chromium(VI) for 30 days. Administration of chromium decreased the body weight and increased organ to body weight ratio significantly. Chromium treatment significantly decreased reduced glutathione (GSH), and increased malondialdehyde (MDA) and creatine phosphokinase (CPK) levels; further it also enhanced glutamate oxaloacetate transferase (GOT) and glutamate pyruvate transferase (GPT) levels in the serum. Different doses of the alcoholic leaf extract of Seabuckthorn were evaluated for the protection against the chromium induced oxidative stress. The results show that the leaf extract at a concentration of 100 and 250mg/kg BW protected the animals from the chromium induced oxidative injury significantly.

Alanine Transaminase↗

Immunomodulatory effects of agents of plant origin.

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.

Adjuvants, Immunologic↗

Anti-oxidant and immunomodulatory properties of seabuckthorn (Hippophae rhamnoides)--an in vitro study.

This study was designed to determine the anti-oxidant and immunomodulatory properties of seabuckthorn (Hippophae rhamnoides) using lymphocytes as a model system. Chromium(VI) as potassium dichromate was used to induce oxidative damage. The production of free radicals by chromium and the ability of alcoholic leaf and fruit extracts of seabuckthorn to inhibit the oxidative damage induced by chromium was investigated. Addition of chromium (10 microg/ml) to the cells resulted in enhanced cytotoxicity, apoptosis, free radical production and decreased glutathione (reduced) levels. Chromium also caused a significant inhibition of lymphocyte proliferation induced by both lipopolysaccharide and concanavalin A. Alcoholic extracts of leaves and fruits of seabuckthorn at a concentration of 500 microg/ml were found to inhibit chromium-induced free radical production, apoptosis, DNA fragmentation and restored the anti-oxidant status to that of control cells. In addition, these extracts also were able to arrest the chromium-induced inhibition of lymphocyte proliferation. These observations suggest that the alcoholic extracts of leaves and fruits of seabuckthorn have marked cytoprotective properties, which could be attributed to the anti-oxidant activity.

Adjuvants, Immunologic↗

Effect of seabuckthorn on sodium nitroprusside-induced cytotoxicity in murine macrophages.

The present study reports the anti-oxidant activity of alcoholic extracts of leaf and fruit of seabuckthorn (SBT) on nitric oxide (NO) induced cytotoxicity in J-774 macrophages. Sodium nitroprusside (SNP), which generates NO at the concentration of 500 microg/ml, induced cytotoxicity as revealed by decreased neutral red uptake by macrophages. The cytotoxicity of SNP was attributed to enhanced reactive oxygen species (ROS) production, which in turn resulted in decrease in anti-oxidant levels. Alcoholic leaf and fruit extracts of SBT at the concentration of 500 microg/ml were found to have a significant cytoprotective effect against SNP-induced oxidative stress. These extracts inhibited SNP-induced cytotoxicity, free radical production and maintained the anti-oxidant status identical to that of control cells. The alcoholic fruit extract of SBT was found to have significantly higher anti-oxidant activity than leaf extract against SNP-induced cytotoxicity in murine macrophages.

Animals↗

Glucocorticoids as prophylaxis against acute mountain sickness.

OBJECTIVE: Acute mountain sickness (AMS) characterized by presence of symptoms including headache, nausea, excessive fatigue, loss of appetite, irritability and insomnia is a major impediment to work performance in human subjects who are rapidly inducted to high altitude (HA) during the initial phase of induction. The present study aims at to evaluate the efficacy of prophylactic administration of low dose glucocorticoids in prevention of AMS in normal healthy men who are inducted to HA by air. DESIGN: Fifty healthy men were randomly divided into five groups of 10 each. Group I received prednisolone (Pred) 10 mg, Group II Pred 20 mg, Group III Pred 40 mg, Group IV dexamethasone 0.5 mg, Group V received placebo once a day in the morning for 2 days at sea level (SL) and for 3 days on arrival at an altitude of 3450 m by air. MEASUREMENTS: The severity of AMS was assessed using Lake Louise AMS scoring system. Physiological parameters like blood pressure, respiratory rate, peripheral blood O2 saturation and heart rate were measured at sea level and on arrival at HA. Circulatory levels of cortisol and adrenocorticotropic hormone (ACTH) were measured by radioimmunoassay (RIA) and immunoradiometreic assay (IRMA), respectively. RESULTS: In the placebo group, significant AMS could be detected at 12 h of arrival at HA, peaked by day 1 or 2 of stay and started declining thereafter. As compared to the placebo group, the steroid treated groups showed a significant (P < 0.01) reduction in daily AMS score. When compared with prednisolone 10 mg, 40 mg and dexamethasone groups, the prednisolone 20 mg group showed an optimal response in reduction of AMS symptoms. The O2 saturation showed a significant decline (P < 0.001) on arrival at HA, but the pattern of O2 saturation in placebo and glucocorticoid groups was identical. Similarly, the rise in heart rate and blood pressure and on day 3 of stay at HA was similar in placebo and glucocorticoid-treated groups. An increase in plasma cortisol in placebo group was observed on day 3 of stay at HA and continued to rise till day 8 of observations. The cortisol levels in Pred 10 mg and Pred 20 mg groups on day 1 and 3 of arrival at HA were not significantly different than the SL post-treatment values but were found to be significantly higher on day 8 of stay. Plasma cortisol in Pred 40 mg and dexamethasone groups was significantly lower (P < 0.01) on day 1 and 3 of stay but showed an increase by day 8 of stay. The ACTH levels were increased at HA in placebo group but did not show any significant change till day 3 of stay in steroid treated subjects and were found to be higher in all groups on day 8 of observations. CONCLUSION: These observations suggest that administration of low-dose glucocorticoids can curtail acute mountain sickness significantly without influencing the normal adreno cortical response to hypoxia.

Acute Disease↗

Hypothalamic-pituitary-adrenal axis following glucocorticoid prophylaxis against acute mountain sickness.

The pituitary-adrenocortical and adrenomedullary response to high altitude (HA) stress was studied following daily single dose administration of prednisolone as a prophylaxis against altitude-induced acute mountain sickness (AMS). Forty healthy men, randomly divided into two groups of twenty, received placebo or prednisolone 20 mg once a day at 08.00 h for two days prior to induction to HA and during an initial three days stay at an altitude of 3450 m. The AMS score and circulatory levels of ACTH, cortisol, epinephrine and norepinephrine were measured at sea level (SL) and during residency at HA. The sensitivity of the hypothalamic-pituitary-adrenal axis in subjects receiving prednisolone therapy was evaluated at SL and on day four of stay at HA. Administration of prednisolone significantly (p < 0.01) decreased the severity of AMS in all the subjects. The steroid dose used did not inhibit endogenous secretion of ACTH, cortisol, epinephrine or norepinephrine, as HA response to adrenocortical and adrenomedullary hormones was identical in placebo and prednisolone treated subjects. The integrity of the hypothalamic-pituitary-adrenal axis was maintained well in subjects receiving low dose prednisolone therapy. These observations suggest that short-term administration of prednisolone is able to curtail AMS without causing suppression of the hypothalamic-pituitary-adrenal axis.

Adrenal Glands↗

Pituitary-gonadal hormones during prolonged residency in Antarctica.

Plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL) and testosterone levels were measured in nine eugonadal men in New Delhi and during the 1st week of different months of their stay at Dakshin Gangotri in Antarctica. During their 12-month stay in Antarctica, they were exposed to a severely cold climate, long polar nights and polar days, high wind velocity, increased amounts of solar and ultraviolet radiation and geomagnetism, as well as physical and social isolation. Plasma testosterone tended to increase in March, but a significant increase (P < 0.05) was not seen until April. The mean testosterone levels in May, June, September and November were also significantly higher than the March or New Delhi values. The absolute values of LH, FSH and PRL did not show any month-to-month changes in Antarctica. However, when the hormone levels were expressed as a percentage of the individual annual Antarctic mean, significant differences as a percentage of the individual annual Antarctic mean, significant differences were observed. The testosterone peak in April, May and June was associated with an increase in LH. The nadirs of testosterone, LH, FSH and PRL were seen in either July or August. FSH showed the highest values in March, whereas the highest PRL values were seen in November. These observations suggest the presence of circannual variations in gonadotropin, PRL and LH in Antarctica which are independent of polar days and polar nights. It appears that factors other than the duration of daylight might be involved in regulating these changes. The significance of maintenance of testosterone levels in the supra-physiological range in Antarctica remains unknown but may be important in acclimatization/habituation to the extreme polar cold by increasing basal metabolic rate, protein synthesis and erythropoiesis.

Acclimatization↗

Plasma insulin and growth hormone during antarctic residence.

Circulatory levels of insulin and growth hormone (GH) were estimated in nine tropical euglycemic men in New Delhi and during the first week of every month of stay in Dakshin Gangotri, Antarctica. Prolonged residency in Antarctica did not alter GH levels because mean GH values during Austral summer and Austral winter were not significantly different from the New Delhi values. Compared with GH, the insulin levels during March, April, and June were found to be significantly lower than the New Delhi values. In Antarctica, the insulin levels in March, April, May, June, July, and August were also found to be significantly lower than the December values. This decline in insulin in Antarctica might be important in increasing substrate availability for heat production by facilitating lipolysis and hepatic glucose output.

Acclimatization↗

Pituitary, gonadal and adrenal hormones after prolonged residence at extreme altitude in man.

High altitude-induced alterations in pituitary, gonadal and adrenal hormones were studied in (i) eugonadal men from the armed forces who were resident at sea level (SL), (ii) SL residents staying at an altitude of 3542 m for periods ranging from 3 to 12 months (acclimatized lowlanders, ALL), (iii) ALL who stayed at 6300 m for 6 months, (iv) ALL who trekked from 3542 to 5080 m and stayed at an altitude of more than 6300 m in the glacier region for 6 months, and (v) high-altitude natives (HAN) resident at an altitude of 3300-3700 m. Circulating levels of LH, FSH, prolactin, cortisol, testosterone, dihydrotestosterone (DHT) and progesterone in ALL at 3542 m and in HAN were not significantly different (p > 0.05) from the SL control values. When the ALL living at 3542 m trekked to an extreme altitude of 5080 m, their testosterone levels showed a significant decrease (p < 0.01) compared to the preceding altitude values but had returned to SL values when measured after 6 months' continuous stay at 6300 m. As with testosterone, the levels of DHT and oestradiol-17 beta (E2) after prolonged stay at extreme altitude were also not significantly different (p > 0.05) from the SL values. The LH levels after trekking to 5080 m were significantly higher (p < 0.01) than at an altitude of 3542 m, but decreased to levels found at 3542 m or SL after prolonged residence at extreme altitude. Plasma levels of ACTH, prolactin, FSH and cortisol on arrival at 5080 m, and after a 6-month stay at extreme altitude, were not significantly different (p > 0.05) from the SL values. Plasma progesterone levels tended to increase on arrival at 5080 m but a significant increase (p < 0.001) was evident only after a 6-month stay at extreme altitude. These observations suggest that prolonged residence at lower as well as at extreme altitude does not appreciably alter blood levels of pituitary, gonadal or adrenal hormones except for plasma levels of progesterone. The exact mechanism and significance of this increase remains unknown, but may be important in increasing the sensitivity of the hypoxic ventilatory response and activation of haemoglobin synthesis.

Acclimatization↗