Introduction: A comparative study of Putranjiva roxburghii Wall. seed extract and developed silver nanoparticles (PJSNPs) for improving bioavailability that enhance their anti-cancer activity against HCT-116 (colon carcinoma), PANC-1 (pancreatic carcinoma), MDA-MB 231 (breast carcinoma) cell lines was performed. Materials and Methods: The green synthesis of PJSNPs (Putranjiva silver nanoparticles) was performed using PJ (Putranjiva) extract, and characterization of synthesized nanoparticles was accomplished through UV-Vis spectrum, X-ray diffraction (XRD), transmission electron microscopy, energy-dispersive X-ray spectroscopy (TEM-EDAX), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), and Raman spectroscopy. Results: The results revealed that PJSNPs are homogeneous, spherical in shape,~8±2 nm in size, and negatively charged with a zeta potential of about −26.71 mV. The cytotoxicity pattern observed was AgNO 3 > PJSNPs > PJ extract. The morphological changes of the cells were observed by flow cytometry and also by the DNA ladder pattern on gel electrophoresis, which indicated that the process of cell death occurred via the apoptosis mechanism and PJSNPs were exerting late-stage apoptosis in all the tested cell lines. The small size and negative value of zeta potential could be the factors responsible for greater bioavailability and thus increased uptake by the tumor cells. Conclusion: The MTT assay and morphological changes observed by various methods indicate that the novel PJSNPs are a better anticancer agent than PJ extract. All the above properties make biologically synthesized PJSNPs an important target in the field of anticancer drug discovery.

1Cellular internalization and intracellular trafficking of particles depend on their specific 2 2 3 1 the sign of cell death whereas, in our study, massive vacuolation by GB did not induce any cell 3 2 death. Moreover, GB treated cells survive with complete vacuolar process, which was reversed 3 3 following post-treatment with vacuole inhibitors in GB treated cells, suggesting normal vacuolar 3 4 function is essential for cell survival. In immunoblotting, upregulation of LC3-II was found in 3 5 GB treated cells. Treatment of the cells with GB was also found to induce translocation of the 3 6 LC3 protein from the nucleus to vacuolar membrane by immune-cytochemistry, indicating LC3 3 7 associated phagocytosis (LAP) like function. This was found to be reversed in the cells treated 3 8 with vacuole inhibitors. The vacuolar function essential for cell survival, preserves mechanistic 3 9correlation with LC3 lipidation on vacuolar membrane, intracellular controlled and slow 4 0 degradation of GB particle and further vacuolar turnover limiting swelling pressure in cells. 4 1 4 2

19The incidence rate of diabetes mellitus is increasing worldwide. Herbal formulations have 20 recently gained importance as an alternative therapeutic option in controlling diabetes without 21 causing any side effects. In the present study, we have demonstrated maintenance of glycemic 22 homeostasis and anti-adipogenic potential of a herbo-mineral formulation Divya MadhuKalp 23 (DMK). Initially, we evaluated the presence of bioactive compounds in DMK using LC/MS-24 QToF analysis. In-vitro analysis of DMK in L6 (skeletal muscle) cells showed a significant 25 increase in cellular glucose uptake. Similarly, a human equivalent dose of DMK significantly 26 reduced blood glucose level in normoglycemic and oral glucose tolerance rat model. DMK 27 extract also inhibited formation of advanced glycation end product and showed anti-α-28 glucosidase activity. Further analysis of DMK in 3T3 L1 pre-adipocytes demonstrated anti-29 adipogenic activity through reduction in intracellular lipid accumulation and triglyceride contents 30 along with downregulation of major adipogenic transcriptional factors (PPAR-γ and C/EBPα) 31 and, adipocytes marker genes (LPL, AP2 and adiponectin). In conclusion, DMK exhibited anti-32 diabetic and anti-adipogenic activities by synergistic effect of its bioactive compounds and can 33 be considered as a potent herbo-mineral formulation for treating metabolic diseases. 34 35 expression. 37 38 39 which may induce unwanted side-effects, natural herbal formulations tend to show similar 63 efficacy with minimal to no side-effects and cost effectiveness 6, 7, 8 . In traditional Indian 64 medicine system, numerous herbal and herbo-mineral formulations have been used for treating 65 various diseases, but their scientific evidence is still lacking. Divya MadhuKalp (DMK) is an 66Ayurvedic herbo-mineral formulation has been extensively used in clinical practices for 67 managing blood glucose levels during onset of DM. The DMK comprises of eight herbs and one 68 minerals-rich organic component in specific proportion to make complex bioactive formulation 69 (Table 1). The ingredients are; Momordica charantia 9 ; Picrorhiza kurroa 10 ; Swertia chiraita 11 ; 70Azadirachta indica 12 ; Trigonella foenum-graecum 13 ; Syzyium cuminii 14 ; Withania somnifera 15 ; 71Aconitum hetrophyllum 16 and Shilajeet (Asphaltum) 17,18 . The ingredients in DMK have been 72 used for diabetic therapy in ancient Indian Ayurvedic medicinal system. In order to explore the 73 pharmacological mechanism of poly herbal extracts, accurate characterization of the bioactive 74 compounds is very essential. Moreover, the quality control is very important factor in discovery 75 of a new drug. LC/MS-QToF technology is most appropriate analytical method for the full 76 characterization and quality control of poly herbal extract 19 . DMK associated herbal ingredients 77 have been found to be rich in secondary metabolite compositions such as, phenolics, terpenes, 78 and nitrogen containing compounds. These active bio-molecules play an important rol...