Thuja occidentalis: An Unexplored Phytomedicine with Therapeutic Applications.

BACKGROUND: The recent outbreak of SARS-CoV-2 has received global attention. Due to a lack of recommended treatment regimens, the world faced various limitations resulting in improper management of the disease. Phytomedicines have played a prominent role in the prevention of various epidemics and pandemics in the past. OBJECTIVE: Here, we attempt to focus on safe and feasible use of Thuja occidentalis to manage and alleviate the panic of viral respiratory infections, including COVID-19, by strengthening an individual's immunity. The relevant information was collected from the web-based databases PubMed, Google Scholar, and MEDLINE, as well as other internet sources to review the applicability of T. occidentalis as a phytomedicine in managing respiratory infections and strengthening immunity. CONCLUSION: As important phytomedicine, and antipsychotic, T. occidentalis possesses a plethora of immunological properties that can be used effectively in the management of viral respiratory infections and has the potential to prevent further progression of the disease. Importantly, this could be only a part of the approach for treatment during the current outbreak that should be considered along with other measures.

Molecular insights into the critical role of gallate moiety of green tea catechins in modulating prion fibrillation, cellular internalization, and neuronal toxicity.

Transmissible spongiform encephalopathies (TSEs) or prion diseases are fatal neurodegenerative diseases with no approved therapeutics. TSE pathology is characterized by abnormal accumulation of amyloidogenic and infectious prion protein conformers (PrPSc) in the central nervous system. Herein, we examined the role of gallate group in green tea catechins in modulating the aggregation of human prion protein (HuPrP) using two green tea constituents i.e., epicatechin 3-gallate (EC3G; with intact gallate ring) and epigallocatechin (EGC; without gallate ring). Molecular docking indicated distinct differences in hydrogen bonding and hydrophobic interactions of EC3G and EGC at the ß2-α2 loop of HuPrP. These differences were substantiated by 44-fold higher KD for EC3G as compared to EGC with the former significantly reducing Thioflavin T (ThT) binding aggregates of HuPrP. Conformational alterations in HuPrP aggregates were validated by particle sizing, AFM analysis and A11 and OC conformational antibodies. As compared to EGC, EC3G showed relatively higher reduction in toxicity and cellular internalization of HuPrP oligomers in Neuro-2a cells. Additionally, EC3G also displayed higher fibril disaggregating properties as observed by ThT kinetics and electron microscopy. Our observations were supported by molecular dynamics (MD) simulations that showed markedly reduced α2-α3 and ß2-α2 loop mobilities in presence of EC3G that may lead to constriction of HuPrP conformational space with lowered ß-sheet conversion. In totality, gallate moiety of catechins play key role in modulating HuPrP aggregation, and toxicity and could be a new structural motif for designing therapeutics against prion diseases and other neurodegenerative disorders.

Comparative Effectiveness of Pre-Identified Homeopathic Medicines in Asymptomatic COVID-19 Individuals Receiving Standard Care-An Open-Label, Randomized, Controlled Exploratory Trial.

BACKGROUND: Asymptomatic COVID-19 subjects can transmit the infection for as many as 14 days and are regarded as a significant factor in the rapid spread of the COVID-19 pandemic. This exploratory study aimed to determine any additional benefits of selected homeopathic medicines compared with placebo in asymptomatic COVID-19 individuals receiving standard care. METHODS: This open-label, randomized, placebo-controlled, exploratory trial was undertaken at a COVID Care Centre (CCC) in Madhya Pradesh, India. Patients (n = 200, 18-65 years, both sexes) having a positive RT-PCR and asymptomatic during admission were enrolled. They were randomly assigned to one of four groups (each n = 50): Arsenicum album 30C (Ars. alb.), Camphora 1M (Camph.), Bryonia alba 30C (Bry. alb.) and placebo (Pl.). All the patients were given standard care. The primary outcome was the number of patients becoming RT-PCR negative for SARS-CoV-2 at days 5, 10 and 15. RESULTS: In total, 200 asymptomatic COVID-19 patients were enrolled. One hundred and seventy-seven patients became RT-PCR negative by day 15; 88%, 80%, 98% and 88% from Ars. alb., Camph., Bry. alb. and Pl. respectively. A Chi-square test of association for the total patients who became RT-PCR negative for SARS-Cov-2 in each group showed a marginal statistical significance (Chi-square: 8.1, p = 0.04). A two-proportion Z-test comparing each pre-identified homeopathic medicine with placebo showed marginal statistical significance (p = 0.05) for Bry alb. only. Median time in days to RT-PCR negative (Kaplan Meier analysis) was 10 days in each of the groups. CONCLUSION: There was some evidence that, compared with Ars alb., Camph. or Pl., Bry. alb. was associated with an increased number of patients who became RT-PCR negative for COVID-19 by day 15. The possible effect exerted needs to be investigated in additional research.

Green Synthesis of Gold Nanoparticles Using Plant Extracts as Beneficial Prospect for Cancer Theranostics.

Gold nanoparticles (AuNPs) have been widely explored and are well-known for their medical applications. Chemical and physical synthesis methods are a way to make AuNPs. In any case, the hunt for other more ecologically friendly and cost-effective large-scale technologies, such as environmentally friendly biological processes known as green synthesis, has been gaining interest by worldwide researchers. The international focus on green nanotechnology research has resulted in various nanomaterials being used in environmentally and physiologically acceptable applications. Several advantages over conventional physical and chemical synthesis (simple, one-step approach to synthesize, cost-effectiveness, energy efficiency, and biocompatibility) have drawn scientists' attention to exploring the green synthesis of AuNPs by exploiting plants' secondary metabolites. Biogenic approaches, mainly the plant-based synthesis of metal nanoparticles, have been chosen as the ideal strategy due to their environmental and in vivo safety, as well as their ease of synthesis. In this review, we reviewed the use of green synthesized AuNPs in the treatment of cancer by utilizing phytochemicals found in plant extracts. This article reviews plant-based methods for producing AuNPs, characterization methods of synthesized AuNPs, and discusses their physiochemical properties. This study also discusses recent breakthroughs and achievements in using green synthesized AuNPs in cancer treatment and different mechanisms of action, such as reactive oxygen species (ROS), mediated mitochondrial dysfunction and caspase activation, leading to apoptosis, etc., for their anticancer and cytotoxic effects. Understanding the mechanisms underlying AuNPs therapeutic efficacy will aid in developing personalized medicines and treatments for cancer as a potential cancer therapeutic strategy.

L-Asparaginase as a new molecular target against leishmaniasis: insights into the mechanism of action and structure-based inhibitor design.

l-Asparaginases belong to a family of amidohydrolases that catalyze the conversion of l-asparagine into l-aspartic acid and ammonia. Although bacterial l-asparaginases have been used extensively as anti-leukemic agents, their possible role as potential drug targets for pathogenic organisms has not been explored. The presence of genes coding for putative l-asparaginase enzymes in the Leishmania donovani genome hinted towards the specific role of these enzymes in extending survival benefit to the organism. To investigate whether this enzyme can serve as a potential drug target against the Leishmania pathogen, we obtained structural models of one of the putative Leishmania l-asparaginase I (LdAI). Using an integrated computational approach involving molecular modelling, docking and molecular dynamics simulations, we found crucial differences between catalytic residues of LdAI as compared to bacterial l-asparaginases. The deviation from the canonical acid-base pair at triad I, along with the structural reorganization of a ß-hairpin loop in the presence of a substrate, indicated an altogether new mechanism of action of the LdAI enzyme. Moreover, the finding of compositional and functional differences between LdAI and human asparaginase was used as a criterion to identify specific small molecule inhibitors. Through virtual screening of a library of 11 438 compounds, we report five compounds that showed favorable interactions with the active pocket of LdAI, without adversely affecting human asparaginase. One of these compounds when tested on cultured Leishmania promastigotes displayed a promising leishmanicidal effect. Overall, our work not only provides first hand mechanistic insights of LdAI but also proposes five strongly active compounds which may prove as effective anti-leishmaniasis molecules.

Development of QSAR model for immunomodulatory activity of natural coumarinolignoids.

Immunomodulation is the process of alteration in immune response due to foreign intrusion of molecules inside the body. Along with the available drugs, a large number of herbal drugs are promoted in traditional Indian treatments, for their immunomodulating activity. Natural coumarinolignoids isolated from the seeds of Cleome viscose have been recognized as having hepatoprotective action and have recently been tested preclinically for their immunomodulatory activity affecting both cell-mediated and humoral immune response. To explore the immunomodulatory compound from derivatives of coumarinolignoids, a quantitative structure activity relationship (QSAR) and molecular docking studies were performed. Theoretical results are in accord with the in vivo experimental data studied on Swiss albino mice. Immunostimulatory activity was predicted through QSAR model, developed by forward feed multiple linear regression method with leave-one-out approach. Relationship correlating measure of QSAR model was 99% (R(2) = 0.99) and predictive accuracy was 96% (RCV(2) = 0.96). QSAR studies indicate that dipole moment, steric energy, amide group count, lambda max (UV-visible), and molar refractivity correlates well with biological activity, while decrease in dipole moment, steric energy, and molar refractivity has negative correlation. Docking studies also showed strong binding affinity to immunomodulatory receptors.