Vanita Gupta

A dose dependent adaptogenic and safety evaluation of Rhodiola imbricata Edgew, a high altitude rhizome

To examine the dose dependent adaptogenic activity aqueous extract of Rhodiola imbricata root was orally administered in rats at different doses, 30 min prior to cold (5 degrees C)-hypoxia (428 mm Hg)-restraint (C-H-R) exposure. The maximal effective adaptogenic dose of the extract was 100 mg/kg body weight. The acute and sub-acute toxicity of the extract was also studied in rats. Sub-acute toxicity studies included administration of single oral dose of 1 g/kg and 2 g/kg of extract once daily for 14 days and maximal effective single oral dose of 100 mg/kg once daily for 30 days. At the end of each treatment period the biochemical parameters related to liver function, kidney function, lipids (triglycerides, cholesterol) and hematological parameters were estimated in serum and blood. Biochemical and hematological analysis showed no significant changes in any of the parameters examined in treated groups animal, in comparison to control animals. No significant change was observed in organ weight/body weight ratios, of any organ studied in comparison to control rats. The oral LD(50) of the extract was observed to be >10 g/kg, indicating an adequate margin of safety. No histopathological changes were observed in the vital organs studied of the treated animals. These results suggest that aqueous extract of R. imbricata root possess potent adaptogenic activity with no acute and sub-acute toxicity.

Anti-oxidative effect of Rhodiola imbricata root extract in rats during cold, hypoxia and restraint (C-H-R) exposure and post-stress recovery.

Anti-oxidative potential of Rhodiola imbricata root aqueous extract was examined in rats, administered orally at a dose of 100 mg/kg both in single and multiple doses, 30 min prior to cold (5 degrees C)-hypoxia (428 mmHg)-restraint (C-H-R) exposure. Lipid per-oxidation, anti-oxidant parameters and lactate dehydrogenase (LDH), were studied in blood, liver and muscle of rats on attaining T(rec)23 degrees C during C-H-R exposure and after recovery (T(rec)37 degrees C) from C-H-R induced hypothermia. The results of untreated control rats on attaining T(rec)23 degrees C showed a significant increase in blood, liver and muscle malondialdehyde (MDA) and LDH levels. Hepatic catalase (CAT) and muscle glutathione S-transferase (GST) also increased significantly. Administration of single dose of Rhodiola imbricata root aqueous extract significantly restricted rise in blood MDA, increased blood reduced glutathione (GSH) and superoxide dismutase (SOD) activity with restricted rise in blood, liver and muscle LDH; improved liver and muscle SOD on attaining T(rec)23 degrees C and T(rec)37 degrees C; liver CAT on attaining T(rec)23 degrees C and liver GST during recovery. Multiple doses treatment of the extract further increased blood, liver and muscle GSH and GST levels; restricted increase in LDH on attaining T(rec)23 degrees C and recovery; increased CAT during recovery. Results suggested the anti-oxidant potential of Rhodiola root extract during C-H-R exposure and post-stress recovery and it also maintained cell membrane permeability.

Anti-stress and Adaptogenic Activity of l-Arginine Supplementation

In the present study, oral supplementation of l-arginine in rats was evaluated for its anti-stress and adaptogenic activity using the cold (5°C)–hypoxia (428 mmHg)–restraint (C-H-R) animal model. A dose-dependent study of l-arginine was carried out at doses of 12.5, 25.0, 50.0, 100.0, 200.0 and 500.0 mg/kg body weight, administered orally 30 min prior to C-H-R exposure. The time taken by the rat to attain a rectal temperature of 23°C (Trec 23°C) during C-H-R exposure and its recovery to Trec 37°C at normal atmospheric pressure and 32 ± 1°C were used as biomarkers of anti-stress and adaptogenic activity. Biochemical parameters related to lipid peroxidation, anti-oxidants, cell membrane permeability, nitric oxide and stress, with and without administration of the least effective l-arginine dose, were measured in rats on attaining Trec 23°C and Trec 37°C. The least effective adaptogenic dose of l-arginine was 100.0 mg/kg body weight. The C-H-R exposure of control rats, on attaining Trec 23°C, resulted in a significant increase in plasma malondialdehyde (MDA), blood lactate dehydrogenase (LDH) and a decrease in blood catalase (CAT) and plasma testosterone levels. On recovery (Trec 37°C) of control rats, there was a further decrease in CAT and plasma testosterone, and an increase in LDH. l-Arginine supplementation resulted in a significant decrease in plasma MDA, an increase in blood superoxide dismutase (SOD), CAT levels maintained at control values and a lower increase in LDH compared with controls (45.3 versus 58.5% and 21.5 versus 105.2%) on attaining Trec 23°C during C-H-R exposure and on recovery to Trec 37°C. The results suggested that l-arginine possesses potent anti-stress activity during C-H-R exposure and recovery from C-H-R-induced hypothermia.

Antistress and Adaptogenic Activity of Lecithin Supplementation

OBJECTIVE Investigation of lecithin administration in rats for its antistress and adaptogenic activity. DESIGN Lecithin was administered orally (1 mg/g body weight) to rats 0.5 hour, 1.5 hours, 3.0 hours, and 6.0 hours prior to cold (5 degrees C)-hypoxia (428 mm Hg)-restraint (C-H-R) exposure and serum choline estimation. The rectal temperature (T(rec)) of the rats was monitored during the exposure and the recovery periods. The time for decrease of T(rec) to 23 degrees C and its recovery to 37 degrees C were used as indices of antistress and adaptogenic activity. RESULTS Lecithin administration 3-6 hours prior to C-H-R exposure was found to have significant adaptogenic activity that correlated with increased serum choline levels. Lecithin administration prior to C-H-R exposure increased the stress tolerance of the rats by delaying the time for decrease of T(rec) to 23 degrees C during C-H-R exposure. It also helped shorten poststress recovery as observed by decreased time to attain T(rec) of 37 degrees C from C-H-R-induced hypothermia (T(rec), 23 degrees C). CONCLUSIONS The results suggested that lecithin supplementation acted as an antistress and adaptogenic functional food. It improved resistance during C-H-R exposure and enhanced recovery from hypothermia.

Podophyllum hexandrum-Mediated Survival Protection and Restoration of Other Cellular Injuries in Lethally Irradiated Mice

This study aims at the development of a safe and effective formulation to counter the effects of lethal irradiation. The sub-fraction (G-001M), prepared from Podophyllum hexandrum has rendered high degree of survival (>90%) at a dose of 6 mg kg−1 body weight (intramuscular) in lethally irradiated mice. Therapeutic dose of G-001M, at about 20 times lower concentration than its LD100, has revealed a DRF of 1.62. Comet assay studies in peripheral blood leukocytes have reflected that, treatment of G-001M before irradiation has significantly reduced DNA tail length (P < .001) and DNA damage score (P < .001), as compared to radiation-only group. Spleen cell counts in irradiated animals had declined drastically at the very first day of exposure, and the fall continued till the 5th day (P < .001). In the treated irradiated groups, there was a steep reduction in the counts initially, but this phase did not prolong. More than 60% decline in thymocytes of irradiated group animals was registered at 5 h of irradiation when compared with controls, and the fall progressed further downwards with the similar pace till 5th day of exposure (P < .001). At later intervals, thymus was found fully regressed. In G-001M pre-treated irradiated groups also, thymocytes decreased till the 5th day but thereafter rejuvenated and within 30 days of treatment the values were close to normal. Current studies have explicitly indicated that, G-001M in very small doses has not only rendered high survivability in lethally irradiated mice, but also protected their cellular DNA, besides supporting fast replenishment of the immune system.

Mechanism of action of Rhodiola imbricata Edgew during exposure to cold, hypoxia and restraint (C-H-R) stress induced hypothermia and post stress recovery in rats

Mechanism of rhodiola root extract adaptogenic activity was studied in rats. The extract was orally administered in rats (100mg/kg body weight), 30 min prior to cold (5 degrees C)-hypoxia (428 mmHg)-restraint (C-H-R) exposure up to fall of T(rec)23 degrees C and recovery (T(rec)37 degrees C) from hypothermia. In untreated control rats serum lactate and non-esterified fatty acids (NEFA) increased on attaining T(rec)23 degrees C with decreased blood enzyme activities hexokinase (HK), phosphofructokinase (PFK), citrate synthase (CS) and glucose-6-phosphate dehydrogenase (G-6-PD), on attaining T(rec)23 degrees C and T(rec)37 degrees C. Decreases were also observed in liver and muscle tissues HK and G-6-PD enzyme activities and liver glycogen and CS on attaining T(rec)23 degrees C and recovery; muscle PFK during recovery; muscle CS on attaining T(rec)23 degrees C. Single and five doses of extract administration restricted increase in serum lactate values of rats on attaining T(rec)23 degrees C and maintained blood NEFA in single dose extract treated animals, indicating improved utilization of NEFA as energy fuel. The single and five doses extract treatment decreased or better maintained tissue glycogen and enzyme activities, viz. HK, PFK, CS and G-6-PD, in blood, liver and muscle, on attaining T(rec)23 degrees C and recovery. The results suggest that rhodiola extract treatment in rats shifted anaerobic metabolism to aerobic, during C-H-R exposure and post stress recovery.

Ninety days of repeated gavage administration of Rhodiola imbricata extract in rats.

Rhodiola imbricata is a high‐altitude plant, possesses adaptogenic, immunomodulatory, anti‐oxidant and cytoprotective activity, and is widely used in traditional medicine. The present study was designed to ascertain the safety of aqueous extract of R. imbricata root when administered by gavage to rats for 90 days. Four groups of animals, each consisting of 15 males and 15 females, were administered 0, 100, 250 or 500 mg kg−1 extract, in a single dose per day. The experimental rats when administered 100 mg kg−1 of extract did not show any significant change in their body weight gain, organ/body weight ratio, or histological, hematological and biochemical variables studied. However, at higher doses of 250 and 500 mg kg−1 extract, an increase in the body weight of rats of both the sexes was apparent without any change in their organ/body weight ratio. Furthermore, a noteworthy increase in plasma glucose and protein levels was recorded at both the higher doses, which were restored to normal after a 2‐week withdrawal of treatment. Based on the findings of this study, the no observed effect level was 100 mg kg−1 body weight per day of aqueous root extract of R. imbricata in rats administered subchronically. Copyright