Social Capital’s Impact on Civic Engagement: An Empirical Study on Pakistani Youth

The aim of this research is to assess the impact of social capital on civic engagement. The quantitative method was applied to measure impact of independent variables on dependent variable. The survey instrument was applied to collected data from undergraduate student of four general Universities of Pakistan. The partial least squares structural equation modeling (PLS-SEM) approach was applied to measure impact of bridging, bonding social capital and trust on civic engagement. Results indicate that bonding social capital and trust have strong association with civic engagement, however, association between bridging social capital and civic engagement was found insignificant. The analyses indicate that it is a basic requirement to bring immediately policy reforms in context of youth development and create more opportunities for youth to engage in the social and structural development of society.

Evaluation of Pharmacological Potential of Bioactive Compounds Isolated from a Selected Medicinal Plant

Plants are rich source of therapeutic compounds that have tremendous applications in the pharmaceutical industry. To identify appropriate plants for isolation of bioactive compounds, methanol/chloroform (M/C) and aqueous (aq.) extracts of 61 medicinal plants were evaluated systematically for their biological activities. Antimicrobial activity was assessed against six bacterial and five fungal strains, while natural antioxidants were studied by using reducing power (RP), total antioxidant capacity (TAC) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Six plants exhibited broad spectrum antibacterial activity while two exerted significant antifungal activity. Antioxidant potential, total phenolic content (TPC) and total flavonoid content (TFC) of plant species varied among extracts as well as in assays used for antioxidant evaluation. Significant linear correlation (p < 0.01) of TPC with antioxidant activities suggested their contribution to antioxidant potential. Based on the results of antimicrobial and antioxidant assays and traditional information Ficus microcarpa was selected for isolation of bioactive compounds. Through chromatographic techniques two pure compounds were isolated from ethyl acetate fraction of Ficus microcarpa and identified through NMR as Plectranthoic acid (PA), a pentacyclic triterpenoid, and 3,4,5,7-Flavantetrol (FL), a flavonoid. These compounds are isolated first time from Ficus microcarpa. Moreover, FL is isolated first time from any natural source. Inhibition of α-glucosidase, α-amylase and dipeptidyl peptidase 4 (DPP-4) is an important therapeutic approach for treating diabetes mellitus (DM). The bioactivity of PA and FL was evaluated to inhibit these enzymes. Among both the compounds, PA possessed pleotropic inhibitory activity with IC50 values of 39.5, 55.5 and 51.4 μM against α-glucosidase, α amylase and DPP-4, respectively. As first line antidiabetic drug metformin activates 5′AMP-activated kinase (AMPK), the potential of PA to enhance AMPK activity was assessed using hepatocytes. AMPK is a well-studied therapeutic target for metabolic syndrome, type-2 diabetes. Our results showed that PA is an activator of AMPK. Epidemiologic studies indicated that diabetics treated with metformin had a lower incidence of cancer than those taking other anti-diabetes drugs. This led to a surge in the efforts to explore the anticancer potential of PA, which has potent AMPK activating properties. We found that treatment of prostate cancer (PCa) cells with PA inhibited proliferation and induced G1 phase arrest in cell cycle that was accompanied with up- Abstract Evaluation of Pharmacological Potential of Bioactive Compounds Isolated from a Selected Medicinal Plant xxiv regulation of cyclin kinase inhibitors p27/KIP1 and p21/CIP1. PA treatment suppressed mTOR/S6K signaling and induced apoptosis in PCa cells in an AMPK-dependent manner. Interestingly, PA-induced autophagy in PCa cells was found to be independent of AMPK activation. Combination studies of PA and metformin demonstrated that metformin had an inhibitory effect on PA-induced AMPK activation and suppressed PA-mediated apoptosis. Then we designed the study to determine the putative targets of PA in PCa cells and employed a quantitative proteomics approach i.e. nano-LC/MS/MS. Results were processed with the SIEVE software to identify proteins with differential expression. A total of 98 unique peptides, showing > 2 fold change, were analyzed by using IPA and PANTHER software’s which identified mTOR pathway is the major canonical pathway. The biological process modulated by PA with the high percentage, i.e. 51.0% proteins, was a metabolic process. Epithelial-to-mesenchymal transition (EMT) plays a crucial role in PCa metastasis. We next identified PA as an inhibitor of EMT which inhibited cell migration, invasion and expression of mesenchymal markers in PCa cells. We presented that PA reverse EMT by using a PCa cell culture model of transforming growth factor-β (TGF-β)-induced EMT. To inhibit migration PA used adherin-junction signalling as a major target and Rac1 was identified as the major protein modulated by PA. PA also affected NEDD9, which activates Rac1 and was identified as a major protein involved in progression and migration of PCa cells. This study identifies plants with antimicrobial and antioxidant properties which could be important for isolation of desired therapeutic compounds and to improve infusions, nutraceuticals and pharmaceuticals. The study suggests that Ficus microcarpa and its isolate PA could be an important natural source for alleviating the symptoms of type 2 DM. Given the anti-proliferative role of PA in cancer and its potent anti-hyperglycemic activity, we suggest that PA should be explored further as a novel activator of AMPK for its ultimate use for the treatment of cancers and inhibition of EMT. This study also deserves further investigation in order to isolate more bioactive secondary metabolites from Ficus microcarpa with anticancer and antidiabetic potential.