Antibacterial potential of Thymus linearis essential oil collected from Wasturwan mountain: A combination of experimental and theoretical studies involving in silico molecular docking simulation of the major compounds against Novobiocin-resistant mutant of DNA Gyrase-B.

Antibiotic resistant bacteria are immune to most antibiotics and are therefore very difficult to treat and in most cases lead to death. As such there is a pressing need for alternative and more efficient antibacterial drugs which can target these drug-resistant strains as well. The objective of this research work was to investigate the antibacterial properties of Thymus linearis essential oil (EO) against multiple disease-causing bacterial pathogens. Additionally, the study aimed to examine the molecular docking and molecular dynamic (MD) simulations of the primary components of the EO with the essential bacterial proteins and enzymes. Gas chromatography-mass spectrometry was employed to analyse the chemical composition of Thymus linearis EO. The initial screening for antibacterial properties involved the use of disc diffusion and microdilution techniques. Molecular docking studies were conducted utilising Autodock Vina. The outcomes were subsequently visualised through BIOVIA Discovery Studio. MD simulations were conducted using iMODS, an internet-based platform designed for MD simulations. The essential oil (EO) was found to contain 26 components, with thymol, carvacrol, p-cymene, and γ-terpinene being the primary constituents. The study findings revealed that Thymus linearis EO demonstrated antibacterial effects that were dependent on both the dose and time. The results of molecular docking studies revealed that the primary constituents of the EO, namely thymol, carvacrol, and p-cymene, exhibited robust interactions with the active site of the bacterial DNA gyrase enzyme. This finding provides an explanation for the antibacterial mechanism of the EO. The results indicate that Thymus linearis EO possesses potent antibacterial properties against the MDR microorganisms. Molecular docking analyses revealed that the essential oil's primary components interact with the amino acid residues of the DNA-Gyrase B enzyme, resulting in a favourable docking score.

Plant based natural products as potential ecofriendly and safer biopesticides: A comprehensive overview of their advantages over conventional pesticides, limitations and regulatory aspects.

The commercially used synthetic pesticides have been proven to be toxic not only to humans and other animals, but also to non-target plant, the surrounding organisms around the plant, and the environment. There are also increased concerns regarding the development of pest resistance towards these synthetic pesticides. As such, biopesticides, which are defined as the certain kinds of pesticides derived from natural sources such as plants, bacteria, fungi, animals and some minerals, are potential alternative pesticides and are gaining increasing attention. Biopesticides are safer and eco-friendly pesticides used for pest management. Among these, plant-based biopesticides constitute a small but important group of biopesticides. Plant based extracts and essential oils have been particularly used in the management of insects exhibiting a variety of anti-insecticidal mechanisms. Their chemical compositions are very complex and as such acquiring resistance by the pest against such biopesticide is very difficult. As far as their mechanism of action is concerned, these can act as insect repellants, insect attractants, or anti-feedants. They can also inhibit respiration or they can obstruct the host plant identification. These insecticides can inhibit oviposition and decrease adult emergence by ovicidal and larvicidal effects. Some of the essential oil based insecticides have even been commercialized for use. However, there are some limitations that restrict the widespread use of such biopesticides. These limitations include cost, difficulties in production, gentle action, and dearth of appropriate biopesticide formulations. As far as their regulations are concerned, it is still a problem in many countries further halting biopesticide use. But one thing is clear that biopesticides do have a promising future due to their eco-friendly nature and unique chemical compositions and unique mode of action.

Gas chromatographic-mass spectrometric analysis, antioxidant, antiproliferative and antibacterial activities of the essential oil of Prangospabularia.

The essential oil composition of the shoot parts of Prangos pabularia, growing in Drass area of Ladakh, India, along with its antioxidant, antibacterial and anticancer activity, is reported for the first time. Gas chromatography coupled with mass spectrometry (GC-MS) revealed the presence of 31 constituents, representing 97.342% of the total essential oil. The major constituents of essential oil were Durylaldehyde (62.161%), Bicyclo [3.1.1] hept-2-en-4-ol (8.846%), Chrysanthenyl acetate (5.120%) followed by unknown (3.420%), (-)-Spathulenol (3.028%), Mesityl aldehyde (2.402%) and Hexahydro farnesyl acetone (1.683%. Cytotoxic activity of the essential oil by MTT assay against human breast adenocarcinoma (MCF7), human breast (HBL-100), human cervical cancer (HELA) and human lung adenocarcinoma epithelial (A549) cells, at four different concentrations (20, 30, 50 & 100 µg/mL) revealed that the activity of 56.12% against A549 (human lung) cell line at 20 µg/mL concentration was the highest. The Essential oil displayed a significant free radical scavenging activity with DPPH. Antibacterial activity was carried out against 3 g positive and 2-g negative bacteria at four different concentrations using Agar Well Diffusion Method taking streptomycin sulphate as reference. The essential oil displayed significant and broad-spectrum antibacterial activity against different bacteria used. The MIC of the oil ranged from 2.06 to 5.00 µg/mL. The zones of inhibition were lesser for Micrococcus and Escherichia coli compared to other strains of bacteria.

Gas Chromatographic-Mass Spectrometric Analysis, Antibacterial, Antioxidant and Antiproliferative Activities of the Needle Essential Oil of Abies pindrow growing wild in Kashmir, India.

The essential oil composition of the leaves of Abies pindrow, growing in Kashmir, India, along with its antioxidant, antibacterial and anticancer activity is reported for the first time. Gas chromatography coupled with mass spectrometry (GC-MS) revealed the presence of 12 constituents, representing 99.9% of the total oil. The major constituents of the oil were limonene (38.9%), α-pinene (36.5%), ß-pinene (6.9%), and α-selinene (4.4%). The essential oil was dominated by the presence of monoterpene hydrocarbons (90.2%), followed by sesquiterpene hydrocarbons (6.761%), oxygenated sesquiterpenes (2.096%) and oxygenated monoterpenes (0.942%). The monoterpene rich essential oil was subjected to antibacterial activity against 4 Gram negative bacteria and 2 Gram positive bacteria at three different concentrations using Agar Well Diffusion Method taking streptomycin sulphate as reference. The oil displayed significant and broad spectrum antibacterial activity against different bacteria used. The minimum inhibitory concentration (MIC) of the active essential oil was determined using Agar Dilution Method. Highest antibacterial activity was shown by the oil against E. Coli (25 mm), and the lowest by Bacillus subtilis (14 mm) and Pseudomonas aeruginosa (14 mm). The oil was subjected to cytotoxic activity by MTT assay against human mammary carcinoma (MCF), human ductal breast epithelial tumour (T47D), human lung adeno-carcinoma epithelial (A549) and rat glial (C6) cell lines at three different concentrations. The results revealed significant sensitization of the cell lines with highest inhibition against human ductal breast epithelial cell line (51%) and the lowest against rat glial cell line (33%) at a concentartion of 50 µg/mL. The oil displayed a significant free radical scavenging activity with DPPH.

Molecular scaffolds from mother nature as possible lead compounds in drug design and discovery against coronaviruses: A landscape analysis of published literature and molecular docking studies.

The recent outbreak of viral infection and its transmission has highlighted the importance of its slowdown for the safeguard of public health, globally. The identification of novel drugs and efficient therapies against these infectious viruses is need of the hour. The eruption of COVID-19 is caused by a novel acute respiratory syndrome virus SARS-CoV-2 which has taken the whole world by storm as it has transformed into a global pandemic. This lethal syndrome is a global health threat to general public which has already affected millions of people. Despite the development of some potential vaccines and repurposed drugs by some Pharma companies, this health emergency needs more attention due to the less efficacy of these vaccines coupled with the emergence of novel and resistant strains of SARS-CoV-2. Due to enormous structural diversity and biological applications, natural products are considered as a wonderful source of drugs for such diseases. Natural product based drugs constitute a substantial proportion of the pharmaceutical market particularly in the therapeutic areas of infectious diseases and oncology. The naturally occurring bioactive antiviral phytochemicals including alkaloids, flavonoids and peptides have been subjected to virtual screening against COVID-19. Since there is no specific medicine available for the treatment of Covid-19, designing new drugs using in silico methods plays an all important role to find that magic bullet which can target this lethal virus. The in silico method is not only quick but economical also when compared to the other conventional methods which are hit and trial methods. Based on this in silico approach, various natural products have been recently identified which might have a potential to inhibit COVID-19 outbreak. These natural products have been shown by these docking studies to interact with the spike protein of the novel coronavirus. This spike protein has been shown to bind to a transmembrane protein called Angiotensin converting enzyme 2 (ACE2), this protein acts as a receptor for the viral spike protein. This comprehensive review article anticipates providing a summary of the authentic and peer reviewed published literature about the potential of natural metabolites that can be developed into possible lead compounds against this new threat of Covid-19. Main focus of the article will be to highlight natural sources of potential anti-coronavirus molecules, mechanism of action, docking studies and the target proteins as well as their toxicity profiles. This review article intends to provide a starting point for the research endeavors that are needed for the design and development of drugs based on pure natural products, their synthetic or semi-synthetic derivatives and standardized plant extracts. This review article will be highly helpful for scientists who are working or intend to work on antiviral drugs from natural sources.

A comprehensive review of the antibacterial, antifungal and antiviral potential of essential oils and their chemical constituents against drug-resistant microbial pathogens.

Essential oils are a complex mixture of odoriferous, volatile organic compounds. There are an extensive number of published articles which highlight the antimicrobial action of a variety of essential oils from various parts of the world. The main aim of this review article is to compile these antimicrobial essential oils and their constituents from reliable sources and put them together. The published literature indicates that essential oils possess a wide-spectrum of antibacterial, antifungal and even anti-viral activity. Essential oils have also been shown to inhibit the growth of drug-resistant microbial strains which are even difficult to be treated by conventional antibiotics. As for as their mode of action is concerned, in fungal pathogens, essential oils establish a membrane potential across cell wall and disrupt ATP assembly, leading to cell wall damage. Essential oils can also disintegrate mitochondrial membrane interfering with the electron transport system (ETS) pathway. In bacterial pathogens, essential oils primarily destabilize the cellular architecture, leading to breakdown of membrane integrity, disrupting many cellular activities including energy production and membrane transport. Membrane rupture induced by essential oils can lead to leakage of cellular components and loss of ions. Several essential oils have antiviral activities against many RNA and DNA viruses, such as type 1 and type 2 herpes simplex virus (HSV-1 and HSV-2), dengue virus type 2, influenza virusadeno virus type 3, poliovirus, Junin virus, and coxsackievirus B1. In conclusion, the current review article discusses in detail the various aspects of antimicrobial activity of essential oils in a comprehensive manner.

Multicomponent phytotherapeutic approach gaining momentum: Is the "one drug to fit all" model breaking down?

Natural product based drugs constitute a substantial proportion of the pharmaceutical market particularly in the therapeutic areas of infectious diseases and oncology. The primary focus of any drug development program so far has been to design selective ligands (drugs) that act on single selective disease targets to obtain highly efficacious and safe drugs with minimal side effects. Although this approach has been successful for many diseases, yet there is a significant decline in the number of new drug candidates being introduced into clinical practice over the past few decades. This serious innovation deficit that the pharmaceutical industries are facing is due primarily to the post-marketing failures of blockbuster drugs. Many analysts believe that the current capital-intensive model-"the one drug to fit all" approach will be unsustainable in future and that a new "less investment, more drugs" model is necessary for further scientific growth. It is now well established that many diseases are multi-factorial in nature and that cellular pathways operate more like webs than highways. There are often multiple ways or alternate routes that may be switched on in response to the inhibition of a specific target. This gives rise to the resistant cells or resistant organisms under the specific pressure of a targeted agent, resulting in drug resistance and clinical failure of the drug. Drugs designed to act against individual molecular targets cannot usually combat multifactorial diseases like cancer, or diseases that affect multiple tissues or cell types such as diabetes and immunoinflammatory diseases. Combination drugs that affect multiple targets simultaneously are better at controlling complex disease systems and are less prone to drug resistance. This multicomponent therapy forms the basis of phytotherapy or phytomedicine where the holistic therapeutic effect arises as a result of complex positive (synergistic) or negative (antagonistic) interactions between different components of a cocktail. In this approach, multicomponent therapy is considered to be advantageous for multifactorial diseases, instead of a "magic bullet" the metaphor of a "herbal shotgun" might better explain the state of affairs. The different interactions between various components might involve the protection of an active substance from decomposition by enzymes, modification of transport across membranes of cells or organelles, evasion of multidrug resistance mechanisms among others.

Induction of apoptosis in human pancreatic MiaPaCa-2 cells through the loss of mitochondrial membrane potential (ΔΨm) by Gentiana kurroo root extract and LC-ESI-MS analysis of its principal constituents.

The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo for antioxidant and antiproliferative activities as well as to study the effect of the extract on the induction of apoptosis in human pancreatic cancer cell line (MiaPaCa-2). The extract exerted significant antioxidant activity as verified by DPPH, hydroxyl radical, lipid peroxidation and protective oxidative DNA damage assays. The results were comparable to standard antioxidants like α-tocopherol, catechin and BHT used in such experiments. Antioxidant potential of G. kurroo may be attributed to the presence of high phenolic and flavonoid content (73±1.02 and 46±2.05 mg/g extract respectively). The anti-proliferative property of Gentiana kurroo root extract was determined by sulphorhodamine B (SRB) assay against Human colon cancer cell line (HCT-116), Lung carcinoma cell line (A-549), Pancreatic cancer cell line (MiaPaCa-2), Lung cancer cell line (HOP-62) and acute monocytic leukaemia cell line (THP-1). G. kurroo root extract inhibited cancer cell growth depending upon the cell line used and in a dose dependent manner. The extract induced potent apoptotic effects in MiaPaCa-2 cells. The population of apoptotic cells increased from 11.4% in case of control to 49.6% at 100 µg/ml of G. kurroo root extract. The extract also induced a remarkable decrease in mitochondrial membrane potential (ΔΨm) leading to apoptosis of cancer cells used. The main chemical constituents identified by the liquid chromatography-tandem mass spectrometry (LC-ESI-MSMS) were found to be iridoid glucosides (iridoids and secoiridoids), xanthones and flavonoids. Iridoid glucosides are the bitter principles of Gentiana species. Loganic acid, Sweroside, Swertiamarin, Gentiopicroside, Gentisin, Isogentisin, Gentioside, Norswertianolin, Swertianolin, 4″-O-ß-D-glucosyl-6'-O-(4-O-ß-D-glucosylcaffeoyl)-linearoside and Swertisin were the principal compounds present in the methanol root extract of G. kurroo.

Chromatographic analysis, anti-proliferative and radical scavenging activity of Pinus wallichina essential oil growing in high altitude areas of Kashmir, India.

PURPOSE: To evaluate the in vitro anti-proliferative and radical scavenging properties of the essential oil and its fractions and to determine the chemo-type of P. wallichiana essential oil. METHOD: Pinus wallichiana oil was extracted by hydro-distillation and fractionated by silica gel column chromatography method. The oil and its fractions were analyzed by Gas chromatography, Gas chromatography-mass spectrometry and (13)C NMR. Different concentrations of oil 12.5, 25, 50 and 100µg/ml and single concentration 50µg/ml of its fractions B(1), B(2), A(2), G(2), Uk(13) and I(2) were evaluated for its anti-proliferative activity by in vitro {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide} assay against human monocyte, lung carcinoma, liver adenocarcinoma, prostate and ovarian carcinoma, while as the radical scavenging activity was evaluated by different in vitro DPPH assays. RESULTS: The analyses indicated the presence of 17 constituents with ß-pinene (46.8%) and α-pinene (25.2%) as major constituents. The oil and its fractions showed significant anti-proliferative activity. The radical scavenging activity also showed good results. CONCLUSION: The oil could be used as a drug to control the diseases like cancer, cirrhosis and arteriosclerosis, caused by reactive oxygen species.

Chemical composition, antioxidant and antibacterial activities of the leaf essential oil of Juglans regia L. and its constituents.

The essential oil from the leaves of Juglans regia L. (Juglandaceae) growing wild in Kashmir (India) was obtained by hydrodistillation and analysed by a combination of capillary GC-FID and GC-MS. A total of 38 compounds, representing 92.7% of the oil, were identified and the major components were found to be α-pinene (15.1%), ß-pinene (30.5%), ß-caryophyllene (15.5%) germacrene D (14.4%) and limonene (3.6%). The essential oil and the main individual constituents were screened for antibacterial activity and the essential oil evaluated for antioxidant activity. Antibacterial activity was evaluated using the disc diffusion and microdilution methods against a group of clinically significant Gram-positive (Staphylococcus epidermidis MTCC-435, Bacillus subtilis MTCC-441, Staphylococcus aureus) and Gram-negative bacteria (Proteus vulgaris MTCC-321, Pseudomonas aeruginosa MTCC-1688, Salmonella typhi, Shigella dyssenteriae, Klebsiella pneumonia and Escherichia coli). The essential oil and its major components exhibited broad spectrum inhibition against all the bacterial strains with Gram-positive being more susceptible to the oil than Gram-negative bacteria. Antioxidant activity of the oil was evaluated by the scavenging effect on DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals. In general, the essential oil exhibited high antioxidant activity which was comparable to the reference standards at the same dose (ascorbic acid and butylated hydroxyl toluene, BHT) with IC(50) values of 34.5 and 56.4µg/ml calculated by DPPH and hydroxyl radical scavenging assays respectively.