Leishmaniasis is a clinical manifestation caused by the parasites of the genus Leishmania. Plants are reservoirs of bioactive compounds, which are known to be chemically balanced, effective and least injurious as compared with synthetic medicines. The current resistance and the toxic effects of the available drugs have brought the trend to assess the antileishmanial effect of various plant extracts and their purified compound/s, which are summarized in this review. Moreover, it also highlights various traditional remedies used by local healers against leishmaniasis. A systematic cross-sectional study for antileishmanial activity of natural products was carried out using multiple literature databases. The records retrieved since 2000 till year 2016 were analysed and summarized in the form of comprehensive tables and graphs. Natural products are potential source of new and selective agents that can significantly contribute to primary healthcare and probably are promising substitutes of chemicals for the treatment of protozoan diseases like leishmaniasis. Where the researchers prefer to use alcoholic solvents for the extraction of antileishmanial agents from plants, most of the studies are limited to in vitro conditions majorly on using promastigote forms of Leishmania. Thus, there is a need to carry out such activities in vivo and in host macrophages. Further, there is a need of mechanistic studies that can help taking few of the promising pure compounds to clinical level. Copyright © 2016 John Wiley & Sons, Ltd.

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In the present study, four different natural compounds including quercetin, gallic acid, rutin, and lupeol were studied for their anti-leishmanial potentials with anticipated mechanism of action through in vitro and in silico approaches. Results showed that rutin was exceedingly active (IC 50 ; 91.2 µg/ml) against the promastigote form of Leishmania tropica compared to quercetin (IC 50 ; 182.3 µg/ml), gallic acid (IC 50 ; 198.00 µg/ml) and lupeol (IC 50 ; 200.77 µg/ml). Similarly, rutin was highly active against the amastigote form as well, followed by quercetin, gallic acid and lupeol with IC 50 values of 101.3 µg/ ml, 137.4 µg/ml, 277.2 µg/ml, and 298.9 µg/ml, respectively. These compounds were found to be nontoxic to human blood erythrocytes even at the highest concentration (1000 µg/ml) tested. Rutin and lupeol showed promising DNA degradation/ fragmentation activity against the DNA of treated promastigotes which increased with the increase in concentration of the compounds. The in silico investigation revealed that these ligands have high affinity with the important catalytic residues of trypanothione reductase (Try-R) where, rutin showed the lowest docking score (i.e., − 6.191) followed by lupeol (− 5.799), gallic acid and quercetin. In case of ligands' interaction with trypanothione synthetase (Try-S), rutin again showed highest interaction with docking score of − 6.601 followed by quercetin (− 4.996), lupeol and gallic acid. The ADMET prediction of these compounds showed that all the parameters were within the acceptable range as defined for human use while molecular dynamics simulation supported the good interaction of quercetin and rutin against both enzymes. These findings suggest that the studied compounds may control leishmanial growth via DNA damage and inhibiting Try-R and Try-S, the two unique but critical enzymes for leishmania growth.

Natural products from plants contain many interesting biomolecules. Among them, quercetin (Q), gallic acid (GA), and rutin (R) all have well-reported antileishmanial activity; however, their exact mechanisms of action are still not known. The current study is a step forward towards unveil the possible modes of action of these compounds against Leishmania donovani (the causative agent of visceral leishmaniasis). The selected compounds were checked for their mechanisms of action against L. donovani using different biological assays including apoptosis and necrosis evaluation, effects on genetic material (DNA), quantitative testing of nitric oxide production, ultrastructural modification via transmission electron microscopy, and real-time PCR analysis. The results confirmed that these compounds are active against L. donovani, with IC50 values of 84.65 µg/mL, 86 µg/mL, and 98 µg/mL for Q, GA, and R, respectively. These compounds increased nitric oxide production and caused apoptosis and DNA damage, which led to changes in the treated cells’ ultrastructural behavior and finally to the death of L. donovani. These compounds also suppressed essential enzymes like trypanothione reductase and trypanothione synthetase, which are critical for leishmanial survival. The selected compounds have high antileishmanial potentials, and thus in-vivo testing and further screening are highly recommended.

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Background:The emerging antimicrobial resistance will be responsible for more casualty by 2050 (AMR review, UK). In this context, a group of antimicrobial resistant ESKAPE pathogen is of prime importance. Methicillin-resistant Staphylococcus aureus is one of the members of ESKAPE pathogens, is clinically important and responsible for various major life-threatening nosocomial infections. Its inherent antibiotic resistance and biofilm-forming capability make it more persistent and difficult to encounter. This scenario will demand to search for new molecules with better antimicrobial and anti-virulence properties against MRSA. Polyalthia longifolia is an ornamental plant containing clerodane diterpenoids (i.e. 16-oxo-cleroda-3, 13( 14) E-diene-15 oic acid (1) and kolavenic acid (2) which posses important pharmacological properties was isolated from leaves of this plant further derivatized to synthetic lactones and studied for their antibacterial and biofilm inhibitory potential.Methods and materials: Compound 1 (16-oxo-cleroda-3, 13(14) E-diene-15 oic acid) and Compound 2 (Kolavanic acid) were isolated from the leaves of Polyalthia longifolia; Compound 1 was further derivatized to synthetic lactones as compound 3, 4, 5 and 6. The isolated compounds and synthetic lactones were screened for their antimicrobial and biofilm inhibition and eradication was evaluated by crystal violet based assay, MTT and calculating CFU/ml. Fluorescence and electron microscopy was conducted to confirm the biofilm inhibitory activities. Molecular mechanism of biofilm inhibition was done by evaluating gene expression analysis by using PCR.Results: Among the tested compounds 1 and 3 were found to have better antistaphylococcal properties with better biofilm inhibiting potential. At 10-30 g/ml 1 and 3 were found to be antivirulence, antibacterial and antibiofilm. Compound 1 was also found to have better biofilm eradicating potential as compared to compound 3. Biofilm inhibitory potential of both the compounds was further confirmed by fluorescence and scanning electron microscopy at MIC and sub MIC levels. Parent compound (1) and its synthetic ␥-lactone (3) significantly delayed the bacterial growth after their short exposure of 10 min. These compounds also altered the gene expression of MRSA biofilm-related genes (icaA). Conclusion:The observed anti-virulence properties and delayed bacterial growth suggested these compounds can be a drug lead to overcome MRSA related infections.

Objective: The purpose of this research is to ascertain the frequency of deeper sections and the diagnostic utility of these sections in non-cutaneous tiny biopsies obtained from a hospital setting. Study Design: Cross-sectional study Place and Duration: This study was carried out at Shaukat Khanum Memorial Hospital Peshawar, Jan 2022 to April 2022 Methods: In this study, there were a total of 100 patients, ranging in age from 16 to 50 years old. Patients who were hospitalized to the oral and maxillofacial department and who had deeper section procedures were considered for inclusion. Following the acquisition of informed and written consent, complete demographic information was obtained. The locations of organs and the levels at which leaks were found were documented for each and every instance. The mean, standard deviation, frequency, and percentages were the metrics that were used to evaluate the categorical variables. All of the data was analysed with SPSS version 22.0. Results: Among the deeper sections, we discovered that cervix cases accounted for 50%, stomach cases accounted for 25%, endometrial cases accounted for 15%, and colorectal cases accounted for 10%. Twenty-six instances 26%, had a deeper section done, with level 4 being the most prevalent. Although in most cases a diagnosis could be determined from the initial slide, in 55 of these cases (55%), further slides were reviewed to look for additional histological features. The goal was to either confirm the diagnosis obtained from the initial slide or raise confidence in that diagnosis. In 55 cases, 39 (70.9%) showed new pathological abnormalities in deeper sections, whereas 16 (29.1%) showed no change in histological features. Conclusion: A more in-depth examination is typically required in order to arrive at a certain diagnosis. Because of this, it is recommended that, regardless of the extent of the lesion, deeper sections be conducted on samples that cannot be consistently detected on ordinary levels, and this approach need to be standardized everywhere in the globe. Keywords: Histopathology, Deeper Sections, Non-cutaneous, Biopsy