Bioactive profiling and evaluation of anti-proliferative and anti-cancerous properties of Shivagutika, an Indian polyherbal formulation synchronizing in vitro and in silico approaches.

Shivagutika is a polyherbal formulation mentioned in Ayurveda, the oldest system of medicine. The aim of this study was to investigate the anti-breast cancer potential of DCM extract of Shivagutika using MCF-7, MDA-MB-231, and MDA-MB-468. Primarily, various extracts of Shivagutika were prepared and subjected to primary in vitro analysis-total protein, phenolic acid content, and flavonoid content. DCM extract among all the extracts showed the promising results hence, it was subjected to LC-MS/MS analysis to identify the phytochemicals. The same extract was subjected to anti-proliferation assay and anti-cancer assay. It inhibited all the 3 cell lines and increased the activity of Caspase 3, pro-apoptotic protein. Further, to find the potent molecule(s) in silico analysis (molecular docking and molecular dynamics simulation studies) was performed. Sciadopitysin was identified as a potent molecule among all phytochemicals as it interacted with Caspase 3 with a binding energy of -7.2 kcal/mol. MD simulation studies also revealed that Sciadopitysin was stable inside the binding pocket of Caspase 3 by interacting with the amino acids in the catalytic site thereby activating the Caspase 3 levels. By all the above results, Shivagutika could be used as a potent anti-breast cancer agent (specifically DCM extract of Shivagutika) which could decrease the cases of breast cancer in future.

New insights on the phytochemical intervention for the treatment of neuropsychiatric disorders using the leaves of Michelia champaca: an in vivo and in silico approach.

CONTEXT: Michelia champaca L. (Magnoliaceae) has been known since ancient times for its rich medicinal properties. OBJECTIVE: The ethanol extract of Michelia champaca leaves (EEMC) was evaluated on depression and anxiety using in vivo and in silico studies. MATERIALS AND METHODS: Swiss albino mice were divided into control, standard, 100 and 200 mg/kg b.w. EEMC groups and for drug administration using oral gavage. The antidepressant activity was evaluated using forced swim test (FST) and tail suspension test (TST) whereas the anxiolytic activity through elevated plus maze and light and dark tests. The in silico studies included molecular docking against human potassium channel KCSA-FAB and human serotonin transporter, and ADME/T analysis. RESULTS: Open arm duration and entries were comparable between 200 mg/kg b.w. group (184.45 ± 1.00 s and 6.25 ± 1.11, respectively) and that of diazepam treated group (180.02 s ± 0.40 and 6.10 ± 0.05, respectively). Time spent in the light cubicle was higher (46.86 ± 0.03%), similar to that of diazepam (44.33 ± 0.64%), suggesting its potent anxiolytic activity. A delayed onset of immobility and lowered immobility time was seen at both the treatment doses (FST: 93.7 ± 1.70 and 89.1 ± 0.40 s; TST: 35.05 ± 2.75 and 38.50 ± 4.10 s) and the standard drug imipramine (FST: 72.7 ± 3.72 and TST: 30.01 ± 2.99 s), indicative of its antidepressant ability. In silico studies predicted doripenem to induce anxiolytic and antidepressant activity by inhibiting human potassium channel KCSA-FAB and human serotonin transporter proteins, respectively. CONCLUSIONS: EEMC is a rich source of bioactive compounds with strong antidepressant and anxiolytic properties.

Evaluation and comparison of anticonvulsant activity of telmisartan and olmesartan in experimentally induced animal models of epilepsy.

BACKGROUND: Epilepsy is one common neurological disorder requiring newer targets and newer drugs for its efficient management. In the recent days brain renin angiotensin system has gained immense importance because of its involvement in seizure regulation. OBJECTIVE: To evaluate and compare antiepileptic activity of different doses olmesartan and telmisartan on MES and PTZ induced seizure models. MATERIALS AND METHODS: Swiss albino mice weighing around 25-30g of either sex were divided into 6 groups: Control ( Distilled Water- 10ml/kg), Standard - Sodium valproate (40mg/kg), O1 - Olmesartan (2.5mg/kg), O2 - Olmesartan (5mg/kg), T1 - Telmisartan (5mg/kg), T2 - Telmisartan (10mg/kg). After 1hour of administration of control , test and standard drugs (orally), convulsions were induced by administering PTZ (70mg/kg - i.p.) in PTZ model. Seizure latency was the parameter recorded. In MES model, suppression of tonic hind limb extension was taken as measure of efficacy. RESULT: The results were analysed by one-way-ANOVA followed by Bonferroni's multiple comparison test. In MES test, dose dependently olmesartan and telmisartan significantly reduced the duration of tonic hindlimb extension in comparison to control (p<0.05). T2 - 9 + 0.89secs significantly reduced the tonic hind limb extension compared to other test groups (p<0.05). The percentage inhibition of seizure was T2-44.3%, O2-28.2%, T1-17.5%, O1- 12.3% respectively. In PTZ test, dose dependently olmesartan and telmisartan produced significant increase in seizure latency (p<0.05). T2 - 206.6+9.83secs significantly increased seizure latency compared to other test groups (p<0.05). Percentage protection from seizure is T2-52.6%, O2- 45.13%, T1- 37.5%, O1- 38.4% respectively. CONCLUSION: AT1 receptor antagonist, telmisartan and olmesartan in a dose dependent manner showed increase in antiepileptic activity. Temisartan at higher dose produced significant antiepileptic activity in comparison to olmesartan.

The effect of carvedilol on blood glucose levels in normal albino rats.

BACKGROUND: Carvedilol is a commonly used drug in hypertension, congestive heart failure in diabetics. It has moderate calcium channel blocking property in addition to α1 and non selective ß antagonistic activity. Though some studies bring forth the beneficial effects of Carvedilol in cardiovascular comorbidities in diabetes, there is no consensus on its effects on glycaemic levels. AIMS: To evaluate the effect of oral Carvedilol administration for 5 days on blood glucose levels in normal albino rats through Oral Glucose Tolerance Test. MATERIAL AND METHODS: Twelve adult albino rats of either sex weighing between 150 - 200 g were selected from central animal facility and randomly divided into 2 groups - Control [Distilled water (1ml/rat orally)] and Test (0.8mg/kg body weight orally) and the respective drugs were administered over 5 days. Following overnight fasting, on the fifth day 1 hour after the last dose of the respective drug, OGTT was performed. The CBG (Capillary Blood Glucose) levels were measured at 0 min, glucose (2g/kg body weight) dissolved in water was administered to all the rats orally. The blood sample from tail vein (obtained by tail snipping) at 60 and 150 minutes were analysed for CBG levels using a standardized glucometer. STATISTICAL ANALYSIS: Data was presented as Mean ± SEM. One way ANOVA, independent samples t-test, non-parametric tests, percentages and cross tabs were used in the analysis of data within the same group and between different groups when required. RESULTS: Carvedilol group showed higher CBG levels at all time intervals of OGTT as compared to the Control group i.e., 0, 60 and 150 minutes, the highest being (103.8±5.029 )mg/dl at 60 minutes and was statistically significant. Carvedilol group however showed lesser inter-interval variation compared to the Control group at the same time intervals respectively but was statistically insignificant. CONCLUSIONS: Carvedilol has hyperglycaemic potential when given orally for 5 days in normal albino rats. Though it may be beneficial in diabetics for various comorbid conditions, the glycaemic control may worsen during its use in subjects with prediabetes, diabetes, high risk diabetes.