Natural Bioenhancers in Drug Delivery: An Overview.

When the bioavailability of a drug increases, a corresponding increase in the levels of that drug in the bloodstream occurs. With this, drug efficacy is augmented and the dosage required to yield a specific therapeutic effect diminishes comparably. Until recently, only a few methods have proven effective in enhancing drug bioavailability, among which are the disaggregation of micronized molecules, the use of timedrelease and topical preparations, mechanization, polymorph and crystal form selection, drug solubilisation, and the use of nanotechnology. (Though still at the experimental stage, nanotechnology promises to become a powerful pharmacological tool in the future.) Bioenhancers are agents not possessing any inherent therapeutic effects but that, when combined with active drugs, potentiate the pharmacological effects of those drugs. Hence the current article describes the enhancement of the bioavailability of drug molecules through the utilization of natural bioenhancers.

The functional pitch of an organ: quantification of tissue texture with photoacoustic spectrum analysis.

PURPOSE: To investigate the use of photoacoustic (PA) spectrum analysis (PASA) to identify microstructural changes corresponding to fat accumulation in mouse livers ex vivo and in situ. MATERIALS AND METHODS: The laboratory animal protocol for this work was approved by the university committee on use and care of animals. Six mice with normal livers and six mice with fatty livers were examined ex vivo with a PA system at 1200 nm, and nine similar pairs of mice were examined at 532 nm. To explore the feasibility of this technique for future study in an in vivo mouse model, an additional pair of normal and fatty mouse livers was scanned in situ with an ultrasonographic (US) and PA dual-modality imaging system. The PA signals acquired were analyzed by using the proposed PASA method. Results of the groups were compared by using the Student t test. RESULTS: Prominent differences between the PASA parameters from the fatty and normal mouse livers were observed. The analysis of the PASA parameters from six normal and six fatty mouse livers indicates that there are differences of up to 5 standard deviations between the PASA parameters of the normal livers and those of the fatty livers at 1200 nm; for parameters from nine normal and nine fatty mouse livers at 532 nm, the differences were approximately 2 standard deviations (P < .05) for each PASA parameter. CONCLUSION: The results supported our hypothesis that the PASA allows quantitative identification of the microstructural changes that differentiate normal from fatty livers. Compared with that at 532 nm, PASA at 1200 nm is more reliable for fatty liver diagnosis. Online supplemental material is available for this article.

Lignans: a versatile source of anticancer drugs.

Background: Cancer is considered as the second deadliest disease globally. Plants have continuously offered unique secondary metabolites with remarkable biological applications. Lignans have gained great importance due to their biological activity. Previous studies revealed that the most remarkable bioactivity of lignan class of molecules is anticancer. They are derived from the oxidative dimerization of two phenylpropanoid units. This review covers the isolated anticancer lignans and their mechanistic aspects. Main body: A bibliographic investigation was performed by analyzing the information available on anticancer lignans in the internationally accepted scientific databases including Web of Science, SciFinder, PubMed, Scopus, and Google Scholar. In this review we have tried to sum up the isolated anticancerous lignan, its source, active plant part, extract and various cell lines used to establish different studies. Here we have included a total number of 113 natural lignans. Many studies that mainly performed in human cell lines have reported. Very few plants have been evaluated for their in vivo anticancer activity. Conclusion: It can be concluded that in near future the lignans may be an effective pharmacon for the treatment of cancer. Fruitful areas of future research may be in modifying natural lignans or synthesizing new lignans with structural diversity and potent pharmacological activities. Extensive studies are needed to be done highlighting the mechanism of anticancer action of explored and unexplored plants. The data will definitely attract many researchers to start further experimentation that might lead to the drugs for the cancer treatment.

Antiepileptic effects of antioxidant potent extract from Urtica dioica Linn. root on pentylenetetrazole and maximal electroshock induced seizure models.

Urtica dioica Linn. (Urticaceae) is a medicinal plant that has shown various therapeutic utilities in folklore medicine along with its use in the treatment of epilepsy. The entire plant has a sensible reservoir of nutritional elements and micronutrients. The purpose of the present study was to investigate the antiepileptic effect of antioxidant potent extract of Urtica dioica root on animal models. Antioxidant activity of various solvent extracts i.e. Petroleum ether extract (PEE), Ethyl acetate extract (EAE), Chloroform extract (CE) and Ethanolic extract (EE) were screened by DPPH radical scavenging assay using Ascorbic acid as the standard. Further the most potent antioxidant extract was subjected to antiepileptic activity against MES and PTZ model. The IC50 values of different Urtica dioica extracts (PEE, CE, EAE, and EE) in antioxidant assay were found to be 167.54 ± 1.97, 134.41 ± 0.82, 88.15 ± 1.39 and 186.38 ± 1.91 µg/ml in DPPH radical scavenging assay, respectively. The EAE has showed the potent antioxidant activity. In experimental study the EAE (100 and 200 mg/kg, p.o) has found to be effective and significant against MES and PTZ induced seizures. The present study also suggested that antioxidant potent extract (EAE) of Urtica dioica root has antiepileptic effect against MES and PTZ induced seizures. However, further research studies will investigate the active component(s) of Urtica dioica responsible for the observed anticonvulsant effects.

DNA-WT1 protein interaction studied by surface-enhanced Raman spectroscopy.

Interactions of proteins with DNA play an important role in regulating the biological functions of DNA. Here we propose and demonstrate the detection of protein-DNA binding using surface-enhanced Raman scattering (SERS). In this method, double-stranded DNA molecules with potential protein-binding sites are labeled with dye molecules and immobilized on metal nanoparticles. The binding of proteins protects the DNA from complete digestion by exonuclease and can be detected by measuring the SERS signals before and after the exonuclease digestion. As a proof of concept, this SERS-based protein-DNA interaction assay is validated by studying the binding of a zinc finger transcription factor WT1 with DNA sequences derived from the promoter of the human vascular endothelial growth factor.

Epitope based vaccine prediction for SARS-COV-2 by deploying immuno-informatics approach.

A new virus termed SARS-COV-2 (causing COVID-19 disease) can exhibit a progressive, fatal impact on individuals. The World Health Organization (WHO) has declared the spread of the virus to be a global pandemic. Currently, there are over 1 million cases and over 100,000 confirmed deaths due to the virus. Hence, prophylactic and therapeutic strategies are promptly needed. In this study we report an epitope, ITLCFTLKR, which is biochemically fit to HLA allelic proteins. We propose that this could be used as a potential vaccine candidate against SARS-COV-2. A selected putative epitope and HLA-allelic complexes show not only better binding scores, but also RMSD values in the range of 0-1 Å. This epitope was found to have a 99.8% structural favorability as per Ramachandran-plot analysis. Similarly, a suitable range of IC50 values and population coverage was obtained to represent greater validation of T-cell epitope analysis. Stability analysis using MDWeb and half-life analysis using the ProtParam tool has confirmed that this epitope is well-selected. This new methodology of epitope-based vaccine prediction is fundamental and fast in application, ad can be economically beneficial and viable.

Cavity resonances of metal-dielectric-metal nanoantennas.

We propose a new design of optical nanoantennas and numerically study their optical properties. The nanoantennas are composed of two cylindrical metal nanorods stacked vertically with a circular dielectric disk spacer. Simulation results show that when the dielectric disk is less than 5nm in thickness, such nanoantennas exhibit two types of resonances: one corresponding to antenna resonance, the other corresponding to cavity resonances. The antenna resonance generates a peak in scattering spectra, while the cavity resonances lead to multiple dips in the scattering spectra. The cavity resonant frequency can be tuned by varying the size of the dielectric disk. The local field enhancement inside the cavity is maximized when the diameter of the dielectric disk is roughly half that of the rod and when the cavity and antenna resonant frequencies coincide with each other. This new nanoantenna promises applications in single molecule surface enhanced Raman spectroscopy (SERS) owing to its high local field enhancements and large scale manufacturability.

Antioxidant-Rich Fraction of Urtica dioica Mediated Rescue of Striatal Mito-Oxidative Damage in MPTP-Induced Behavioral, Cellular, and Neurochemical Alterations in Rats.

Parkinson's disease (PD) having a complex and multi-factorial neuropathology includes mainly the degeneration of the dopaminergic nigrostriatal pathway, which is a cumulative effect of depleted endogenous antioxidant enzymes, increased oxidative DNA damage, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. The present study was designed to investigate the neuroprotective effect of a potent antioxidant from Urtica dioica in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. MPTP was administered intranigrally for the induction of PD in male Wistar rats. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical, cellular, and neurochemical parameters were measured. Intranigrally repeated administration of MPTP showed significant impairment of motor co-ordination and marked increase of mito-oxidative damage and neuroinflammation in rats. Intranigral MPTP significantly decreases the dopamine and its metabolites with impairment of dopaminergic cell density in rat brain. However, post-treatment with the potent antioxidant fraction of Urtica dioica Linn. (UD) (20, 40, 80 mg/kg) improved the motor function, mito-oxidative defense alteration significantly and dose dependently in MPTP-treated rats. In addition, the potent antioxidant fraction of UD attenuated the pro-inflammatory cytokines (TNF-α and IL-ß) and restored the level of dopamine and its metabolites in MPTP-induced PD in rats. Moreover, minocycline (30 mg/kg) with lower dose of UD (20 mg/kg) had significantly potentiated the protective effect of minocycline as compared to its effect with other individual drug-treated groups. In conclusion, Urtica dioica protected the dopaminergic neurons probably by reducing mito-oxidative damage, neuroinflammation, and cellular alteration along with enhanced neurotrophic potential. The above results revealed that the antioxidant rich fraction of UD contain flavonoids and phenolic compounds, which have a promising approach in therapeutics of PD.

Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant) in CCl4 challenged rats.

The aim of the present study was to isolate hepatoprotective component from Urtica dioica Linn. (whole plant) against CCl4-induced hepatotoxicity in-vitro (HepG2 cells) and in-vivo (rats) model. Antioxidant activity of hydro alcoholic extract and its fractions petroleum ether fraction (PEF), ethyl acetate fraction (EAF), n-butanol fraction (NBF) and aqueous fraction (AF) were determined by DPPH and NO radicals scavenging assay. Fractions were subjected to in-vitro HepG2 cell line study. Further, the most potent fraction (EAF) was subjected to in-vivo hepatoprotective potential against CCl4 challenged rats. The in-vivo hepatoprotective active fraction was chromatographed on silica column to isolate the bioactive constituent(s). Structure elucidation was done by using various spectrophotometric techniques like UV, IR, 1H NMR, 13C NMR and MS spectroscopy. Ethyl acetate fraction (EAF) of hydro-alcoholic extract of U. dioica possessed the potent antioxidant activity viz. DPPH (IC50 78.99 ± 0.17 µg/ml) and NO (IC50101.39 ± 0.30 µg/ml). The in-vitro HepG2 cell line study showed that the EAF prevented the cell damage. The EAF significantly attenuated the increased liver enzymes activities in serum and oxidative parameters in tissue of CCl4-induced rats, suggesting hepatoprotective and anti-oxidant action respectively. Column chromatography of most potent antioxidant fraction (EAF) lead to the isolation of 4-hydroxy-3-methoxy cinnamic acid (ferulic acid) which is responsible for its hepatoprotective potential. Hence, the present study suggests that EAF of hydro-alcoholic extract has significant antioxidant and hepatoprotective potential on CCl4 induced hepatotoxicity in-vitro and in-vivo.