Antioxidant and Antimicrobial Screening of Isolated Alkaloids from Tinospora crispa

The antioxidant capacity by DPPH radical scavenging and antimicrobial activity by disk diffusion and broth microdilution method of nine isolated alkaloids from T. crispa were evaluated. All isolated alkaloids had been divided into three groups which were aporphine alkaloids, N-formylannonaine (1), N-formylnornuciferine (2), magnoflorine (9), oxoaporphine alkaloids, lysicamine (3) and liriodenine (4); and protoberberine alkaloids, columbamine(6), dihydrodiscretamine (7) and 4,13-dihydroxy-2,8,9-trimethoxydibenzo [a,g]quinolizinium (8). Protoberberine alkaloids showed (IC50 > 500-800 μg/mL) radical scavenging activity while oxaporphine alkaloids inhibited the growth of the Gram-positive bacteria, Staphylococcus aureus (+) and Enterococcus faecalis (+).The antioxidant and antimicrobial properties of different compounds support documented traditional use of T. crispa in wound healing and treatment of rheumatic, diarrhoea, ulcers, itches and wounds. Results of the present biological activity investigation further points to the potential of this plant species as a good source of natural antioxidant and preservative in food industry.

Nanotechnology-Based Strategies for Berberine Delivery System in Cancer Treatment: Pulling Strings to Keep Berberine in Power

Cancer is a multifactorial disease characterized by complex molecular landscape and altered cell pathways that results in an abnormal cell growth. Natural compounds are target-specific and pose a limited cytotoxicity; therefore, can aid in the development of new therapeutic interventions for the treatment of this versatile disease. Berberine is a member of the protoberberine alkaloids family, mainly present in the root, stem, and bark of various trees, and has a reputed anticancer activity. Nonetheless, the limited bioavailability and low absorption rate are the two major hindrances following berberine administration as only 0.5% of ingested berberine absorbed in small intestine while this percentage is further decreased to 0.35%, when enter in systemic circulation. Nano-based formulation is believed to be an ideal candidate to increase absorption percentage as at nano scale level, compounds can absorb rapidly in gut. Nanotechnology-based therapeutic approaches have been implemented to overcome such problems, ultimately promoting a higher efficacy in the treatment of a plethora of diseases. This review present and critically discusses the anti-proliferative role of berberine and the nanotechnology-based therapeutic strategies used for the nano-scale delivery of berberine. Finally, the current approaches and promising perspectives of latest delivery of this alkaloid are also critically analyzed and discussed.

Yellow Medicine of Nature- The future Chartbuster Protoberberine Antivirals

Emerging viral diseases are one of the principal threat towards the plants, animals and humans. Viruses are fast evolving, resulting in reduced effectiveness of existing drugs and vaccines. At this juncture, the importance of traditional medicine, as well as medicinal plant active principles, occupies central attention of researchers across the world. Protoberberine alkaloids, an essential group of isoquinoline family of alkaloids, exhibit properties were affecting the life cycle of DNA and RNA viruses. However, from this protoberberine group, only berberine alkaloid has been studied in detail for its mechanism of action. Berberine is useful both in the case of enveloped and non-enveloped viruses. Berberine inhibits viral life cycle by modulating NF-kB signalling, targeting viral glycoproteins and downregulation of MEK-ERK signalling. Apart from this, berberine also inhibits ACE. All protoberberine alkaloids share a characteristic protoberberine skeleton. The protoberberine containing botanicals also exhibited antiviral properties. Therefore protoberberine alkaloids and protoberberine containing botanicals are interesting to experiment in detail for their antiviral properties and mechanism of action in emerging viral diseases of plants, animals and humans.

Ligand Selectivity in the Recognition of Protoberberine Alkaloids by Hybrid-2 Human Telomeric G-Quadruplex: Binding Free Energy Calculation, Fluorescence Binding, and NMR Experiments

The human telomeric G-quadruplex (G4) is an attractive target for developing anticancer drugs. Natural products protoberberine alkaloids are known to bind human telomeric G4 and inhibit telomerase. Among several structurally similar protoberberine alkaloids, epiberberine (EPI) shows the greatest specificity in recognizing the human telomeric G4 over duplex DNA and other G4s. Recently, NMR study revealed that EPI recognizes specifically the hybrid-2 form human telomeric G4 by inducing large rearrangements in the 5′-flanking segment and loop regions to form a highly extensive four-layered binding pocket. Using the NMR structure of the EPI-human telomeric G4 complex, here we perform molecular dynamics free energy calculations to elucidate the ligand selectivity in the recognition of protoberberines by the human telomeric G4. The MM-PB(GB)SA (molecular mechanics-Poisson Boltzmann/Generalized Born) Surface Area) binding free energies calculated using the Amber force fields bsc0 and OL15 correlate well with the NMR titration and binding affinity measurements, with both calculations correctly identifying the EPI as the strongest binder to the hybrid-2 telomeric G4 wtTel26. The results demonstrated that accounting for the conformational flexibility of the DNA-ligand complexes is crucially important for explaining the ligand selectivity of the human telomeric G4. While the MD-simulated (molecular dynamics) structures of the G-quadruplex-alkaloid complexes help rationalize why the EPI-G4 interactions are optimal compared with the other protoberberines, structural deviations from the NMR structure near the binding site are observed in the MD simulations. We have also performed binding free energy calculation using the more rigorous double decoupling method (DDM); however, the results correlate less well with the experimental trend, likely due to the difficulty of adequately sampling the very large conformational reorganization in the G4 induced by the protoberberine binding.