The combination of the active principles of Podophyllum hexandrum supports early recovery of the gastrointestinal system via activation of Nrf2-HO-1 signaling and the hematopoietic system, leading to effective whole-body survival in lethally irradiated mice.

This study is aimed at the development of a safe radioprotective formulation to minimize human sufferings during accidental nuclear exposures. In the current study, a combination of three active principles, namely podophyllotoxin, podophyllotoxin beta-D-glucoside, and rutin (G-002M), isolated from Podophyllum hexandrum rhizomes, has been evaluated for its radioprotective potential and mode of action. Total body protection studies have demonstrated that a single prophylactic dose of G-002M delivered more than 85% survival in mice exposed to a lethal (9 Gy) dose of gamma radiation, and significantly protected the radiosensitive hematopoietic and gastrointestinal organs. Studies have also revealed a reduction in free radical generation, lipid peroxidation, protein carbonylation, and cell death in mouse intestine after G-002M treatment, while GSH was observed to be enhanced in the same tissue. Redox-sensitive transcription factor (Nrf2) activation and subsequent upregulation of heme oxygenase-1 (HO-1) and SOD-1 revealed the cytoprotective role of G-002M. A histological examination of the jejunum pretreated with the formulation also demonstrated less damage to the villi, crypts, and the mucosal layers. These observations reiterated that the reduction in the ROS levels, protection of cellular macromolecules, and activation of the antioxidant signaling pathway may have been the principle factors involved in G-002M- mediated protection against radiation-induced tissue impairment. The potentially safe and effective radioprotective characteristics of this new combination are encouraging for further studies for human application.

The nuances of atherogenic dyslipidemia in diabetes: focus on triglycerides and current management strategies.

Diabetes mellitus (DM) is a pandemic disease and an important cardiovascular (CV) risk factor. The atherogenic dyslipidemia in diabetes (ADD) is characterized by high serum triglycerides, high small dense LDL levels, low HDL levels and postprandial lipemia. Insulin resistance is a primary cause for ADD. Though statins are highly effective for CVD prevention in DM but a significant residual CV risk remains even after optimal statin therapy. Fibrates, niacin and omega-3 fatty acids are used in addition to statin for treatment of ADD (specifically hypertriglyceridemia). All these drugs have some limitations and they are far from being ideal companions of statins. Many newer drugs are in pipeline for management of ADD. Dual PPAR α/γ agonists are in most advanced stage of clinical development and they have a rational approach as they control blood glucose levels (by reducing insulin resistance, a primary factor for ADD) in addition to modulating ADD. Availability of dual PPAR α/γ agnosits and other drugs for ADD management may improve CV outcomes and decrease morbidity and mortality in diabetic patients in future.

Bioavailability, antioxidant and non toxic properties of a radioprotective formulation prepared from isolated compounds of Podophyllum hexandrum: a study in mouse model.

The current study was aimed to determine the stability, serum protein binding ability, biodistribution, antioxidant potential and tissue toxicity status of a novel radioprotective formulation (G-002M) from Podophyllum hexandrum. G-002M is the combination of a flavonoid, a lignan and its glucoside isolated from P. hexandrum rhizome that exhibit high radioprotective potential. Stability of G-002M tagged with 99mTc was observed in vitro and with mice serum till 24 hr of incubation. The formulation was investigated for its antioxidant status and its bioavailability and toxicity in different organs of mice. Biodistribution study of 99mTc-G-002M revealed its uptake by all the vital organs of mice. Higher absorbed dose was observed in lungs, liver, jejunum and kidney. Maximum retention of G-002M in kidney revealed that G-002M was excreted predominantly through renal route. G-002M was also observed to have high free radical scavenging and total reducing properties. Histopathological observations showed no significant alterations in tissue morphology of lungs, liver, jejunum and kidney by G-002M administration. The data conclusively demonstrate that high stability, multi organ availability, longer retention and non-toxic behavior of G-002M might help in exhibiting strong protective potential against lethal radiation.

Hypertension with elevated levels of oxidized low-density lipoprotein and anticardiolipin antibody in the circulation of premenopausal Indian women chronically exposed to biomass smoke during cooking.

UNLABELLED: This study aims to investigate whether indoor air pollution (IAP) from biomass fuel use was associated with hypertension, platelet hyperactivity, and elevated levels of oxidized low-density lipoprotein (oxLDL) and anticardiolipin antibody (aCL). We enrolled 244 biomass fuel-using (median age 34 year) and 236 age-matched control women who cooked with liquefied petroleum gas (LPG). Enzyme-linked immunosorbent assay was used to measure oxLDL in plasma and aCL in serum, flow cytometry for P-selectin expression on platelet and reactive oxygen species (ROS) generation by leukocytes, aggregometry for platelet aggregation, spectrophotometry for superoxide dismutase (SOD) in erythrocytes, and laser photometer for particulate matter <10 and 2.5 µm in diameter (PM(10) and PM(2.5), respectively) in cooking areas. Biomass users had three times more particulate pollution in kitchen, had higher prevalence of hypertension (29.5 vs. 11.0% in control, P < 0.05), elevated oxLDL (170.6 vs. 45.9 U/l; P < 0.001), platelet P-selectin expression (9.1% vs. 2.4%), platelet aggregation (23.2 vs. 15.9 Ohm), raised aCL IgG (28.7% vs. 2.1%), IgM (8.6% of vs. 0.4%), and ROS (44%) but depleted (13%) SOD. After controlling potential confounders, the changes were positively associated with PM(10) and PM(2.5) in indoor air, suggesting a positive association between IAP and increased cardiovascular risk. PRACTICAL IMPLICATIONS: The study showing high risk of developing cardiovascular diseases (CVD) among poor, underprivileged women in their reproductive ages in rural India is important from public health perspectives. It may motivate the government and the regulatory agencies of the country to take a serious note of the indoor air pollution (IAP) from biomass fuel use as it threatens the health of millions of women, children, and the elderly who mostly stay indoor. We hope the findings will strengthen the demand for setting up a standard for indoor air quality in the country in the line of national ambient air quality standard. The findings may also inspire the authorities to take measures for the reduction in IAP by improving housing, kitchen ventilation, and cook stoves. Moreover, the parameters used in this study can be utilized for large, population-based studies to identify women at a higher risk of developing CVD so that medical intervention can be taken at the formative stage of a disease.

Inhibition in radiation mediated cellular toxicity by minimizing free radical flux: one of the possible mechanisms of biological protection against lethal ionizing radiation by a sub- fraction of Podophyllum hexandrum.

The study has focused on exploring the mechanism of action of Podophyllum hexandrum sub-fraction (G-001M) exhibiting >90% protection in lethally irradiated mice. Currently, G-001M was assessed for antioxidant characteristics by evaluating DPPH, superoxide and hydrogen peroxide radical formation, anti-lipid per oxidation, metal chelation and total flavonoid content. To affirm cytoprotective efficacy of G-001M, plasmid DNA protection, blood WBC counts, marker for lipid peroxidation (MDA) and antioxidant status (GSH) in mice splenocytes and thymocytes were studied. G-001M, having high amount of total phenolic contents (200±10mg, w/w), exhibited dose dependent inhibition in DPPH and superoxide radical formation. Hydrogen peroxide radical scavenging was higher than standards. With pre-treatment of G-001M, plasmid DNA was also maximally restored to supercoiled form. Radiation modulated MDA and GSH values in splenocytes and thymocytes of mice altered significantly after 24 hrs and at later intervals, values were close to the controls. Radiation mediated losses in WBC counts were significantly regained (p<0.001) in G-001M pre-treated irradiated mice. The above findings explicitly conveyed that G-001M has successfully minimized radiation inflicted free radicals generation and their multiplication. This activity of G-001M could be undoubtedly among one of the major modes of action in extending whole body survival in lethally irradiated mice.

Aqueous extract of Rhodiola imbricata rhizome inhibits proliferation of an erythroleukemic cell line K-562 by inducing apoptosis and cell cycle arrest at G2/M phase.

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.

Management of chronic hepatitis B with New Livfit in end stage renal disease.

New Livfit (NLF) is a standardized, poly-herbal formulation that has been found useful in the management of hepatitis. The aim of this placebo-controlled study was to evaluate its usefulness against hepatitis B virus in the patients of end stage renal disease (ESRD). Patients were regularly evaluated at 6, 12, 24 and 36 weeks of therapy. With 36 weeks of treatment of NLF, there was rapid clearing of HBV-DNA in a significant number of patients. Significant seroconversion of the other markers of hepatitis B and restoration of the raised levels of ALT and AST was observed. The study suggests the potential usefulness of NLF in the control of HBV infection in the patients of ESRD prior to renal transplant.

Rational design and synthesis of novel 2,5-disubstituted cis- and trans-piperidine derivatives exhibiting differential activity for the dopamine transporter.

Herein, we report the rational design and synthesis of novel 2,5-disubstituted piperidine derivatives in the cis and trans isomeric forms. Out of these two isomers, the cis-isomer, 7a, was found to exhibit the most potent activity and selectivity for the dopamine transporter. These novel derivatives represent conformationally constrained version of piperidine analogue of GBR compounds.

Genotoxicity of sennosides on the bone marrow cells of mice.

Preparations of a number of plants which contain hydroxyanthraquinones as active constituents are used worldwide for their laxative effect. Anthraquinone glycosides of Cassia angustifolia and C. fistula were investigated for their ability to induce a clastogenic effect on the bone marrow cells of Swiss albino mice. The endpoints screened were chromosomal aberrations and frequency of aberrant cells. Oral exposure to doses of these anthraquinones and their equivalent amount in leaf and pod extracts did not induce significant numbers of chromosomal aberrations or aberrant cells. The results indicate that anthraquinone sennoside B and rhein are weakly genotoxic.

Efficacy of oral hyposmolar glucose-based and rice-based oral rehydration salt solutions in the treatment of cholera in adults.

BACKGROUND: Recent animal experiments and clinical trials have shown that both osmolarity and rice as the organic components are important factors for net intestinal absorption of an oral rehydration salt solution. METHODS: In a controlled clinical trial 123 male adult patients with severe cholera, after initial rehydration with intravenous Ringer's lactate solution, were randomly assigned to receive one of the four oral rehydration salt solutions: WHO ORS, ORS containing 70 mmol/l Na+ and 16.2 g/l glucose, rice ORS containing 50 g/l rice and 90 mmol/l Na+, and rice ORS containing 50 g/l rice and 70 mmol/l Na+. All patients received 300 mg of doxycycline as a single dose. RESULTS: Patients who received rice-low-sodium ORS subsequently had lower (P < 0.05) stool output, ORS consumption, and diarrhoea duration than the other three ORS groups. CONCLUSIONS: We conclude that rice-based low-sodium ORS is superior for treating adult cholera.

Hydroalcoholic human placental extract: skin pigmenting activity and gross chemical composition.

BACKGROUND: Vitiligo is a pigmentary disorder of the skin of unknown etiology. It is thought to be of autoimmune origin after demonstration of antibody-mediated destruction of melanocytes. Photochemotherapeutic PUVA therapy is widely used in vitiligo with about 33% success. Aqueous or hydroalcoholic extracts of human placenta of ill-defined composition have also been used therapeutically for vitiligo. A hydroalcoholic human placental extract has been developed by us with pigmenting activity based on experimental therapies. Its chemical analysis was the primary objective of this study. METHODS: For the guinea pig experiment, 20 drops of the extract or vehicle (60% alcohol) as control was topically applied around the nipples covering the areola zones of male immature white guinea pigs (wt. 175-250 g) daily for 60 days with 15 minutes infrared (IR) exposure used for vascular dilatation and enhancement of the absorption of the extract. Standard methods have been followed for all chemical analyses. RESULTS: The guinea pig experiment showed clear pigmentation and hypertrophy of the experimental nipples to varying degrees. Chemical analysis of the extract revealed the presence of small-molecular-weight proteins/peptides, lipids (including glycosphingolipids), carbohydrates, sialic acids, cholesterol, triglycerides, high density lipoproteins (HDL), and others, including amino acids, nucleotides, carotenes, vitamins, etc. CONCLUSION: Glycosphingolipids, known modulators of B and T cells, were reported capable of inducing adhesion, spreading, and motility of melanoma. It is present in the extract and, therefore, may lead to skin pigmentation through induction of melanocytes. Endothelin, a 21-amino acid peptide, detected in human placenta and possibly extractable by our process, has been reported to be indispensable for melanocyte growth.

Phototherapy induced hypocalcemia.

Sixty neonates with hyperbilirubinemia were included in the study. There were 20 preterm (Group A) and 20 full term (Group B) neonates. Ten neonates from each group formed the control group. The study group neonates were managed with phototherapy while the control group neonates were not subjected to phototherapy. Serum calcium levels of the two groups were studied. Ninety per cent preterm neonates and seventy-five per cent full term neonates developed hypocalcemia after being subjected to phototherapy. There was a highly significant fall in the total as well as ionized calcium levels in the study group in contrast to the control group. It is recommended that neonates under phototherapy should be given supplemental calcium to prevent hypocalcemia.

Some ayurvedic important plants from district kamrup (assam).

The authors while on ethnobotanical study tour to the district of Kamrup (Assam) collected the following medicinal plants from Ayurvedic point of view and studied other economic values which is presented in this paper.

Filaricidal properties of a wild herb, Andrographis paniculata.

Water decoction of the leaves of Andrographis paniculata killed in vitro the microfilaria of Dipetalonema reconditum in 40 min. Three subcutaneous injections of the extract into infected dogs at 0.06 ml per kg body-weight reduced the number of microfilariae in blood by more than 85%. The larvae were not totally eliminated with more infections but the reduced microfilarial level persisted. No toxic effect of the extract was observed in rabbits. The treated dogs became lethargic initially for a week, probably due to the mass killing of microfilariae.