Zingiber roseum Roscoe. (Zingiberaceae): Current and future perspective

Introduction: A perennial, aromatic, tuberose plant Zingiber roseum (Roscoe.) (Zingiberaceae), flourishes in tropical and subtropical climates. In Traditional Chinese Medicine, several pharmacological properties of Zingiber roseum have been reported its antiseptic, antivertigo, and antidiarrheal activities. Therefore, the present article aims to provide insights into the ethnomedicinal, phytochemistry, and pharmacology of Zingiber roseum. Methods: The literature was compelled after systematically searching scientific databases, including Scopus, PubMed, Google Scholar, and Research Gate. The selection criteria for the plant comprised the therapeutic potential of Zingiber roseum and its active components. Moreover, to explore anti-diabetic activity, ligands of interest from Z. roseum were evaluated for their affinity towards PPAR-α and PPAR-γ. Results and discussions: Out of 200 articles, 140 were selected for the current study, and from the para-topic literature, it was found that Zingiber roseum has numerous pharmacological properties due to the presence of phytoconstituents like flavonoids, alkaloids, phenolic chemicals, terpenoids, saponins, and phytosterols. Furthermore, in silico studies were carried out using PyRx. It was found that rosmarinic acid (-8.3 kcal/mol) and stigmasterol (-11.12 kcal/mol) exhibited the highest binding affinities for PPAR-α and PPAR-γ, respectively, when compared to standard Rosiglitazone. Conclusion: It may be concluded that Z. roseum has several therapeutic activities. Moreover, in silico studies revealed the anti-diabetic action of Z. roseum via modulation of PPAR-α and PPAR-γ

FDG-PET findings in fronto-temporal dementia: A case report and review of literature

Fronto-temporal lobar degeneration (FTLD) is a clinically and pathologically heterogeneous syndrome, characterized by progressive decline in behavior or language associated with degeneration of the frontal and anterior temporal lobes. Three distinct clinical variants of FTLD have been described. Despite the difficulties, accurate diagnosis is critical because the clinical management differs for Alzheimer's disease (AD) and FTLD. Positron emission tomography with fluro-deoxy-glucose (FDG-PET) typically shows sufficient abnormalities that can be used to improve the accuracy of distinguishing AD from FTLD in individual cases. Though temporo-parietal hypometabolism is sensitive in diagnosis of AD, it is less specific. The importance of evaluating the cingulate and anterior temporal cortices for arriving at a diagnosis of FTLD is stressed

Advanced case of PKDL due to delayed treatment: A rare case report.

Post-kala-azar dermal leishmaniasis (PKDL) is clinical outcome of visceral leishmaniasis (VL) and is thought to be the potential reservoir of parasite. Miltefosine (MF) is the only oral drug existing for treatment of post-kala-azar dermal leishmaniasis (PKDL). Increased miltefosine tolerance in clinical isolates of Leishmania donovani has been reported and is one of the major concerns in the treatment of PKDL. Here, we report a highly ulcerated PKDL case that was successfully cured after miltefosine treatment

Bispidine-Amino Acid Conjugates Act as a Novel Scaffold for the Design of Antivirals That Block Japanese Encephalitis Virus Replication

<div><h3>Background</h3><p>Japanese encephalitis virus (JEV) is a major cause of viral encephalitis in South and South-East Asia. Lack of antivirals and non-availability of affordable vaccines in these endemic areas are a major setback in combating JEV and other closely related viruses such as West Nile virus and dengue virus. Protein secondary structure mimetics are excellent candidates for inhibiting the protein-protein interactions and therefore serve as an attractive tool in drug development. We synthesized derivatives containing the backbone of naturally occurring lupin alkaloid, sparteine, which act as protein secondary structure mimetics and show that these compounds exhibit antiviral properties.</p> <h3>Methodology/Principal Findings</h3><p>In this study we have identified 3,7-diazabicyclo[3.3.1]nonane, commonly called bispidine, as a privileged scaffold to synthesize effective antiviral agents. We have synthesized derivatives of bispidine conjugated with amino acids and found that hydrophobic amino acid residues showed antiviral properties against JEV. We identified a tryptophan derivative, Bisp-W, which at 5 µM concentration inhibited JEV infection in neuroblastoma cells by more than 100-fold. Viral inhibition was at a stage post-entry and prior to viral protein translation possibly at viral RNA replication. We show that similar concentration of Bisp-W was capable of inhibiting viral infection of two other encephalitic viruses namely, West Nile virus and Chandipura virus.</p> <h3>Conclusions/Significance</h3><p>We have demonstrated that the amino-acid conjugates of 3,7-diazabicyclo[3.3.1]nonane can serve as a molecular scaffold for development of potent antivirals against encephalitic viruses. Our findings will provide a novel platform to develop effective inhibitors of JEV and perhaps other RNA viruses causing encephalitis.</p> </div

Underlying image data for the corrected Fig 2D (correct DMSO panel from the original experiment).

Underlying image data for the corrected Fig 2D (correct DMSO panel from the original experiment).</p

Synthesis of Bisp-W derivatives and its effect on JEV.

<p>(A) Structure of Bisp-W derivatives with tryptophan on one arm of bispidine and benzyl on the other (Bisp-W-Benzyl) and with Boc group deprotected (Bisp-W-NH). (B) Viral titers were determined by plaque assay of N2A cell culture supernatants (22 h pi) infected with JEV and treated with 5 µM derivatives of Bisp-W as indicated. *** P = 0.0003 and 0.0004 and ns: not significant (P = 0.425) as determined by two-tailed, t-test. Error bars represent Mean ± SEM of three replicates. Data are representative of experiments performed twice with three replicates.</p

Synthesis of amino acid conjugates of bispidine.

<p>(A) Structure of bispidine conjugated with tryptophan (Bisp-W), lecine+phenylalanine (Bisp-LF) and lysine (Bisp-K). (B) Viral titers were determined by plaque assay of N2A cell culture supernatants (22 h pi) infected with JEV and treated with 5 µM of derivatives of bispidine. *** P = 0.0004 and 0.0004, ** P = 0.0034 and as determined by two-tailed, t-test. Error bars represent Mean ± SEM of three replicates. (C) Cytotoxicity was measured by lactate dehydrogenase (LDH) assay from culture supernatants treated with 5 µM of the indicated bispidine conjugates or DMSO. LDH released from cells incubated with detergent buffer was used as 100% LDH release. (D) IC₅₀ value for Bisp-W in the indicated cell lines was estimated by measuring viral titers in cell culture supernatants (22 h pi) infected with JEV and treated with the indicated concentration of Bisp-W. Error bars represent Mean ± SEM of three replicates. All the data are representative of experiments performed at least twice with three replicates.</p

Bisp-W blocks JEV RNA replication.

<p>(A) Viral titers were determined by plaque assay of N2A cell culture supernatants (22 h pi) infected with JEV and treated with DMSO or 5 µM of Bisp-W at the indicated time points. Error bars represent Mean ± SEM. ** P<0.005, **** <0001, * <0.01, ** 0.096 and ** <0.001 for respective time points. (B) Viral titers were determined by plaque assay of N2A cell culture supernatants infected with JEV and treated with PBS or 20 µM minocycline and DMSO or 5 µM of Bisp-W as described in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002005#s2" target="_blank">materials and methods</a>. Error bars represent Mean ± SEM. *** P = 0.0002. N.D: Not Detected. (C) Western blot analysis of N2A lysates prepared from JEV-infected and DMSO or Bisp-W-treated cells. C- Capsid. β–actin is shown for loading control. (D) Viral titers were determined from supernatants (extracellular) and cell lysates (intracellular) at 22 h pi by plaque assay of samples from N2A cells infected with JEV and treated with 5 µM of Bisp-W at 1 h post-infection. ***P = 0003 and 0.00002 respectively. (E) Total RNA was isolated from N2A cells infected with JEV and treated with 5 µM Bisp-W at 1 h post-infection. JEV genome copy numbers were estimated by quantitative real time PCR normalized to GAPDH mRNA. ** P = 0.0001 by unpaired two-tailed t-test. Error bars represent Mean ± SEM. Data are representative of two or more experiments performed with three replicates.</p