Effect of metformin on serum vitamin B12 and red blood cell indices in North Indian subjects with diabetes mellitus

Background:Diabetes mellitus(DM)affecting almost half a billion people worldwide and India is amongst the top ten countries of adults with diabetes. Metformin, the first-line therapy for diabetes, is associated with vitamin B12 malabsorption and subsequently, the development of vitamin B12 deficiency/insufficiency could manifest severe complications like neuropathy or anemia in the future. This study evaluatedthe effect of metformin on vitamin B12 and RBC indices in the North Indian population.Methods:This study was executed at a tertiary care hospital. 35 T2DM(type 2 DM)participants with ongoing metformin therapy were compared with 27 T2DM participants without metformin therapy. Participants were recruited from outpatient after diagnosis as per American diabetes association(ADA)criteria.Results:Metformin-treated participants had significantly low hemoglobin (t=2.096, df=60, 0.0403) compared to untreated participants. Similarly, MCHC was significantly lower in the metformin group (mean=33.28 gm/dl) compared to non-metformin group (mean=34.53 gm/dl) (t=2.745, df=60, p=0.0080). Moreover, there was a strong negative correlation (r=-0.4613, p=0.0053) among vitamin B12 and MCV in metformin group. There was no statistically significant correlation between vitamin B12 and RBC indices (MCV, MCH, MCHC) in the non-metformin group. Analyzing contingency table (Fisher抯 exact test), we found no major difference (p=0.2002) between two groups of vitamin B12 with an odds ratio of 2.026 (95% CI=0.7366 to 5.633). Unpaired ttest also confirmed insignificancy (t=0.04077, df=60, p=0.9676).Conclusions:Strong negative correlation was observed between vitamin B12 and MCV. Despite the insignificant difference of vitamin B12 between metformin and non-metformin groups, significantly lowMCHC was found in metformin-treated participants.

Sedative and muscle relaxant activities of diterpenoids from Phlomidoschema parviflorum

Abstract Phlomidoschema parviflorum (Benth.) Vved. (Basionym: Stachys parviflora Benth.) Lamiaceae, have significance medicinal importance as it is used in number of health disorders including diarrhea, fever, sore mouth and throat, internal bleeding, weaknesses of the liver and heart genital tumors, sclerosis of the spleen, inflammatory tumors and cancerous ulcers. The present contribution deals with the sedative and muscle relaxant like effects of diterpenoids trivially named stachysrosane and stachysrosane, isolated from the ethyl acetate soluble fraction of P. parviflorum. Both compounds (at 5, 10 and 15 mg/kg, i.p) were assessed for their in vivo sedative and muscle relaxant activity in open field and inclined plane test, respectively. The geometries of both compounds were optimized with density functional theory. The molecular docking of both compounds were performed with receptor gamma aminobutyric acid. Both compounds showed marked activity in a dose dependent manner. The docking studies showed that both compounds interact strongly with important residues in receptor gamma aminobutyric acid. The reported data demonstrate that both compounds exhibited significant sedative and muscle relaxant-like effects in animal models, which opens a door for novel therapeutic applications.

Development, characterization and antioxidant activity of polysorbate based O/W emulsion containing polyphenols derived from Hippophae rhamnoides and Cassia fistula

The objective of this study was to develop a pharmaceutical O/W emulsion containing plant-derived polyphenol extracts and evaluate its stability and antioxidant activity. O/W emulsions were prepared using ionic surfactant polysorbate 80 (Tween 80®). The odorwas adjusted with few drops of blue sea fragrance. DPPH (1,1-diphenyl-2-picrylhydrazyl) assay was used to evaluate the antioxidant activity of the plant extracts alone and emulsions containing these extracts. Physical stability was assessed by submitting the emulsions to storage at 8 ºC, 25 ºC, 40 ºC and 40 ºC + 70% RH (relative humidity) for two months. Various physical characteristics of emulsions monitored, include color, creaming, liquefaction, centrifugation and pH. Brookfield rotational rheometer was used to determined viscosities and rheological behavior of emulsions. Different types of emulsion were determined microscopically, while pH values of emulsions were measured by a pH meter. Electrical conductivity data confirmed that the outer phase was water. Samples presented an acceptable pH value for an external topical use. Shear thinning behaviour was observed for all emulsions. The polyphenol-rich-plant-derived extracts alone and the extract containing emulsions showed good antioxidant activities. This research confirmed that the method used was suitable for preparing emulsions with Hippophae rhamnoids and Cassia fistula extracts, suggesting that those emulsions are suitable for topical use.

O presente estudo objetivou o desenvolvimento de uma emulsão farmacêutica óleo-água contendo extratos de plantas ricos em polifenóis, a comparação à sua formulação-controle e a avaliação de sua estabilidade, assim como de sua capacidade antioxidante. Extrato concentrado de Hippophae rhamnoids e Cassia fistula foi encapsulado no interior da fase oleosa da emulsão O/W. As emulsões foram preparadas usando o tensoativo iônico monooleato sorbital de polioxietileno (Tween 80®). O odor foi ajustado pela adição de algumas gotas de fragrância azul do mar. O ensaio do DPPH (1,1-difenil-2-picrilidrazil) foi utilizado para avaliar a atividade antioxidante dos extratos de plantas sozinhos e nas emulsões contendo os extratos. A estabilidade física foi avaliada submetendo os cremes a diferentes temperaturas de estocagem, como a 8 ºC, 25 ºC e 40 ºC e a 40% + 70% de umidade relativa por um período de 2 meses. As características físicas das emulsões foram monitoradas por 2 meses incluindo cor, cremosidade, liquefação, centrifugação e pH. O reômetro rotacional de Brookfield foi utilizado para determinar a viscosidade e o comportamento reológico das emulsões. O programa Rheocalc Brookfield foi utilizado para análise dos dados. As características organolépticas também foram avaliadas. O tipo de emulsão foi determinado microscopicamente, enquanto o pH das emulsões foi avaliado por meio de um pHmetro. A estabilidade farmacêutica esperada das emulsões foi alcançada dentro dos dois meses de estudo. Os resultados da condutividade elétrica confirmaram que a fase externa da emulsão era composta de água. O pH das amostras estava dentro da normalidade para uso tópico. A emulsão apresentou boa fragrância e pode ser retirada da pele com água após a aplicação, características desejáveis em emulsões O/W. Os extratos vegetais ricos em polifenóis isolados ou nas emulsões apresentaram boa atividade antioxidante. Nossos estudos confirmaram que o método utilizado foi adequado para preparar a emulsão semi-sólida contendo extratos de Hippophae rhamnoids e Cassia fistula. Nossos achados sugerem que emulsões contendo extratos de Hippophae rhamnoids e Cassia fistula são adequados para o uso tópico.

In vivo screening of essential oils of Skimmia laureola leaves for antinociceptive and antipyretic activity

Objective:To study the screening of essential oils of Skimmia laureola leaves (SLO) for acute toxicity, antinociceptive, antipyretic and anticonvulsant activities in various animal models. Methods: SLO were extracted using modified Clevenger type apparatus. Acute toxicity test was used in mice to observe its safety level. Antinociceptive activity of SLO was evaluated in acetic acid induced writhing and hot plate tests. Yeast induced hyperthermic mice and pentylenetetrazole induced convulsive mice were used for the assessment of its antipyretic and anticonvulsant profile respectively. Results: Substantial safety was observed for SLO in acute toxicity test. SLO showed a high significant activity in acetic acid induced writhing test in a dose dependent manner with maximum pain attenuation of 68.48%at 200 mg/kg i.p. However, it did not produce any relief in thermal induced pain at test doses. When challenged against pyrexia evoked by yeast, SLO manifested marked amelioration in hyperthermic mice, dose dependently. Maximum anti-hyperthermic activity (75%) was observed at 200 mg/kg i.p. after 4 h of drug administration. Nevertheless, SLO had no effect on seizures control and mortality caused by pentylenetetrazole. Conclusions:In vivo studies of SLO showed prominent antinociceptive and antipyretic activities with ample safety profile and thus provided pharmacological base for the traditional uses of the plant in various painful conditions and pyrexia. Additional detail studies are required to ascertain its clinical application.