Cardioprotective Activity of Cassia fistula L. Bark Extract in Isoproterenol-Induced Myocardial Infarction Rat Model.

Cassia fistula Linn, generally recognized as Indian laburnum, is one of the ancient trees in the Indian subcontinent used for its ornamental and diverse medicinal properties. It is known for its ethnic medicinal uses in inflammatory and infectious pathologies such as antihelmintic, purgative, carminative, antipyretic, expectorant, analgesic, laxative, antiseptic, and antidote against snake poison. The Cassia bark is rich in anthraquinones, flavanols glycosides, and sitosterols, which renders it cardioprotective properties. The existing experiments were designed to assess the potential of Cassia fistula bark against isoproterenol (ISP)-induced cardiotoxicity in rats, which has not been validated yet. The bark was successively extracted with five different solvents, and each extract was subjected to in vitro antioxidant studies. Further acute oral toxicity assays were carried out preceding in vivo myocardial studies. Cardiotoxicity-inducing agent, ISP, was administrated to the rats for two consecutive days (8th and 9th). Based on in vitro studies, the Cassia fistula methanolic extract (CFME) was administered in two doses: CFME-LD (lower dose 250 mg/kg) and CFME-HD (high dose 500 mg/kg) separately. It was found that CFME produced a substantial decrease in lipid peroxidation and an increase in antioxidants in myocardial tissues. CFME abrogated the levels of triglyceride and total cholesterol with a decrease in alanine transaminase (ALT) and aspartate transaminase (AST) activity in serum at both doses. 2,3,5-Triphenyltetrazolium chloride (TTC) staining and histopathology also revealed the protective effects of CFME against ISP-induced myocardial infarction. The study showed the significant role of the CFME as a strong antioxidant and cardioprotective action in ISP-induced toxicity.

Clerodendrum serratum extract attenuates production of inflammatory mediators in ovalbumin-induced asthma in rats.

In the present study, ethanolic extract of Clerodendrum serratum roots was investigated for its potential to reverse some features of bronchial asthma in ovalbumin-induced murine model of asthma. Clerodendrum serratum commonly called bharangi, (family Solanaceae) is a well-known anti-allergic drug in Asian folk system of medicines. In the present work, pharmacological studies are done to provide scientific evidence for therapeutic potential of plant in allergic asthma. Asthma was induced in experimental rats with allergen suspension of ovalbumin and aluminum hydroxide followed by treatment with dexamethasone (2.5 mg/kg, po) or C. serratum root extract (0.53 and 5.3 mg/kg, b. w., po). Biomarkers of inflammatory response including cell counts, immunoglobulin E, cytokines such as interleukin (IL) -4, -5, -1ß, tumor necrosis factor-α (TNF-α), leukotriene (LTD-4), and nitrite concentration in blood as well as bronchial (BAL) fluid were tested. Lung functions in asthmatic and treated animals were evaluated as breathing rate and tidal volume. Treatment with C. serratum extract markedly (p < 0.001, p < 0.01, and p < 0.05) diminished infiltration of inflammatory cells, IgE, cytokines, and nitrites in blood serum and bronchial fluid. Improvement in lung functions (p < 0.05) of asthmatic animals after CSE treatment also supports our findings. Results of the study suggest therapeutic potential of C. serratum in allergic asthma that can be related to ability of plant to attenuate response of inflammatory cells and thereby, production of inflammatory and proinflammatory cytokines in airways.

Synthesis, ADMET prediction and reverse screening study of 3,4,5-trimethoxy phenyl ring pendant sulfur-containing cyanopyrimidine derivatives as promising apoptosis inducing anticancer agents.

Cancer remains considered as one of the leading global health problems either due to meagre and suboptimal therapeutic response of chemotherapeutic agents or due to the emergence of spontaneous complex multidrug resistance in cancer cells. This created a persistent need for the development of new anticancer agents. Enthralled by the high success rate for natural product-based drug discovery and current research scenario, we synthesized a new series of 3,4,5-trimethoxy phenyl ring pendant sulfur-containingcyanopyrimidine derivatives clubbed with different amines intending to search an anticancer lead compound. To probe the anti-proliferative spectrum of the synthesized derivatives, an in-vitro evaluation was piloted against a panel of 60 cancer cell lines at the National Cancer Institute (NCI) representing major types of cancer diseases. Most of the derivatives showed good to moderate anti-proliferative activity. The results revealed that compound 4e displayed the most promising broad-spectrum anticancer activity with high growth inhibition of various cell lines representing multiple cancers diseases. Mechanistic investigation of compound 4e in human breast cancer MDA-MB-231 cells showed that compound 4e triggers cell death through the induction of apoptosis. ADMET studies and reverse screening were also performed to identify the potential targets of designed molecules. It was concluded that 3,4,5-trimethoxy phenyl ring pendant sulfur-containingcyanopyrimidine derivative 4e could act as a promising hit molecule for further development of novel anticancer therapeutics.

Antidiabetic activity of hydro-alcoholic stem bark extract of Callicarpa arborea Roxb. with antioxidant potential in diabetic rats.

BACKGROUND: Despite the availability of synthetic antidiabetic drugs, diabetes mellitus is still affecting millions of people with increasing rate of disease incidence and mortality throughout the world. Ethnomedicinal survey documents the traditional usefulness of Callicarpa arborea Roxb. stem bark in the management of diabetes mellitus. MATERIALS AND METHODS: In our study, hydro-alcoholic extract (HAE) of Callicarpa arborea stem bark was prepared according to WHO guidelines for herbal drugs, and screened for antidiabetic activity in streptozotocin (STZ)-induced diabetic rats. Acute oral toxicity and in vitro antioxidant activity studies along with phytochemical analyses of HAE were also carried out. RESULTS: Acute oral toxicity study indicated that HAE was safe up to a dose of 2000mg/kg body weight of rats. Results of antidiabetic activity study revealed that HAE of C. arborea stem bark possesses significant (p<0.05) hypoglycemic activity compared to normal control group in experimental rats. Histological observations of treated pancreas and liver tissues confirmed the antidiabetic efficacy of HAE. In antioxidant activity, HAE exhibited significant radical scavenging activity. CONCLUSION: From results, it can be concluded that HAE of C. arborea stem bark may have possible role as herbal antioxidants in the prevention and/or treatment of oxidative stress-induced diabetes mellitus. The antioxidant property of plant phenolic and flavonoid contents present in HAE might be responsible for the antidiabetic efficacy of C. arborea stem bark.

Design, virtual screening and docking study of novel NS3 inhibitors by targeting protein-protein interacting sites of dengue virus - a novel approach.

Currently dengue is a serious disease which has become a global burden in the last decade. Unfortunately, there are no effective drugs and vaccines against this disease. DENV non-structural protein (NS) 3, which is viral protease which is a potential target for antiviral therapy. Targeting this we performed homology modeling and protein-protein docking study of NS3 with NRBP (Nuclear Receptor Binding Protein) of human as it has been proved that NS3 of DENV interacts with NRBP which causes cellular trafficking in human cell. To carry out search of novel DENV protease inhibitors by in silico screening panduratin molecule was selected. 65 novel compounds were designed which involved substituting positions 1-5 of the benzyl ring A (4hydroxy-panduratinA) with various substituents. The protein-protein docking showed that the aminoacid residues of NS3 which were interacting with NRBP were found to be Ala 325, Asp 324, Phe 326, Asp 335, Glu 336, Glu 328, Asp 485, Gln 478, Arg 459, Gly 446 and Leu 480. These residues were targeted by the ligands which showed excellent binding affinity as binding energy. The ligand PKP10 showed lowest binding energy. It is also observed that the interface residues participated in the protein-protein interaction are being inhibited by the ligands.