Mechanism of antibacterial phytoconstituents: an updated review.

The increase of multiple drug resistance bacteria significantly diminishes the effectiveness of antibiotic armory and subsequently exaggerates the level of therapeutic failure. Phytoconstituents are exceptional substitutes for resistance-modifying vehicles. The plants appear to be a deep well for the discovery of novel antibacterial compounds. This is owing to the numerous enticing characteristics of plants, they are easily accessible and inexpensive, extracts or chemicals derived from plants typically have significant levels of action against infections, and they rarely cause serious adverse effects. The enormous selection of phytochemicals offers very distinct chemical structures that may provide both novel mechanisms of antimicrobial activity and deliver us with different targets in the interior of the bacterial cell. They can directly affect bacteria or act together with the crucial events of pathogenicity, in this manner decreasing the aptitude of bacteria to create resistance. Abundant phytoconstituents demonstrate various mechanisms of action toward multi drug resistance bacteria. Overall, this comprehensive review will provide insights into the potential of phytoconstituents as alternative treatments for bacterial infections, particularly those caused by multi drug resistance strains. By examining the current state of research in this area, the review will shed light on potential future directions for the development of new antimicrobial therapies.

In Silico Analysis of PTP1B Inhibitors and TLC-MS Bioautography-Based Identification of Free Radical Scavenging and α-Amylase Inhibitory Compounds from Heartwood Extract of Pterocarpus marsupium.

Type 2 diabetes mellitus leads to metabolic impairment caused by insulin resistance and hyperglycemia, giving rise to chronic diabetic complications and poor disease prognosis. The heartwood of Pterocarpus marsupium has been used in Ayurveda for a long time, and we sought to find the actual mechanism(s) driving its antidiabetic potential. Methanol was used to prepare the extract using a Soxhlet extraction, and the identification of metabolites was performed by thin-layer chromatography (TLC) and ultraperformance-liquid chromatography and mass spectroscopy (UP-LCMS). The antioxidant potential of methanolic heartwood extract of Pterocarpus marsupium MHPM was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and a reducing power assay. The α-amylase and α-glucosidase enzyme inhibitory potential of MHPM were investigated for their antidiabetic activity against acarbose. TLC-MS-bioautography was performed to identify the compounds responsible for possible antioxidant and antidiabetic activities. Moreover, targeting protein tyrosine phosphatase 1B (PTP1B), a key regulator of insulin resistance, by identified metabolites from MHPM through molecular docking and all-atom molecular dynamics (MD) simulations was also undertaken, suggesting its potential as an antidiabetic herb. The IC50 of free-radical scavenging activity of MHPM against DPPH was 156.342 ± 10.70 µg/mL. Further, the IC50 values of MHPM in α-amylase and α-glucosidase enzymatic inhibitions were 158.663 ± 10.986 µg/mL and 180.21 ± 11.35 µg/mL, respectively. TLC-MS-bioautography identified four free radical scavenging metabolites, and vanillic acid identified by MS analysis showed both free radical scavenging activity and α-amylase inhibitory activity. Among the identified metabolites from MHPM, epicatechin showed significant PTP1B docking interactions, and its MD simulations revealed that PTP1B forms a stable protein-ligand complex with epicatechin throughout the progression, which indicates that epicatechin may be used as a promising scaffold in the development of the antidiabetic drug after isolation from Pterocarpus marsupium. Overall, these findings imply that Pterocarpus marsupium is a source of valuable metabolites that are accountable for its antioxidant and antidiabetic properties.

Heartwood Extract of Pterocarpus marsupium Roxb. Offers Defense against Oxyradicals and Improves Glucose Uptake in HepG2 Cells.

Diabetes mellitus leads to cellular damage and causes apoptosis by oxidative stress. Heartwood extract of Pterocarpus marsupium has been used in Ayurveda to treat various diseases such as leprosy, diabetes, asthma, and bronchitis. In this study, we worked out the mechanism of the antidiabetic potential of methanolic heartwood extract of Pterocarpus marsupium (MPME). First, metabolic profiling of MPME was done using gas chromatography-mass spectrometry (GCMS), ultra-performance liquid chromatography-mass spectroscopy (UPLC-MS), and high-performance thin-layer chromatography (HPTLC) to identify phenols, flavonoids, and terpenoids in MPME. Biological studies were carried out in vitro using the HepG2 cell line. Many antidiabetic compounds were identified including Quercetin. Methanolic extract of MPME (23.43 µg/mL-93.75 µg/mL) was found to be safe and effective in reducing oxyradicals in HepG2 cells. A concentration of 93.75 µg/mL improved glucose uptake efficiently. A significant decrease in oxidative stress, cell damage, and apoptosis was found in MPME-treated HepG2 cells. The study suggests that the heartwood of Pterocarpus marsupium offers good defense in HepG2 cells against oxidative stress and improves glucose uptake. The results show the significant antidiabetic potential of MPME using a HepG2 cell model. The effect seems to occur by reducing oxidative stress and sensitizing the cells towards glucose uptake, hence lowering systemic glucose levels, as well as rescuing ROS generation.

Metabolomic Profiling and Identification of Antioxidant and Antidiabetic Compounds from Leaves of Different Varieties of Morus alba Linn Grown in Kashmir.

Mulberry (Morus alba L.) is commonly cultivated in Asian countries as a traditional medicine and food supplement. Four Kashmiri Morus alba varieties (Zagtul, Chtattatual, Chattatual Zaingir, and Brentul Kashmir) were evaluated for their proximate composition, mineral content, total phenolic and flavonoid content, antioxidant potential, and antihyperglycemic activity. Furthermore, TLC-MS-bioautography was used for the identification of antioxidant and antidiabetic compounds in the best active extract. Lastly, UPLC-MS was employed for metabolomic profiling of the best variety of M. alba. Among all the varieties, the Zagtul variety was found to have the highest phenolic (71.10 ± 0.44 mg GAE/g DW) and flavonoid (53.22 ± 0.69 mg rutin/g DW) content. The highest antioxidant potential (DPPH) with an IC50 value of 107.88 ± 3.8 µg/mL was recorded for the Zagtul variety. Similarly, α-amylase and α-glucosidase inhibition for antidiabetic potential with IC50 74.76 ± 6.76 and 109.19 ± 5.78 µg/mL, respectively, was recorded in Zagtul variety. TLC-MS-bioautography for identification of bioactive compounds revealed the presence of chlorogenic acid for antioxidant potential and 1-deoxynojirimycin (DNJ) and syringic acid for antidiabetic potential. Further, bioactive compounds responsible for diverse functions of M. alba were confirmed by UPLC-MS in both negative and positive modes. However, major compounds in the Zagtul variety were identified as chlorogenic acid, moracin N, gallic acid, ferulic acid, morin, 1-deoxynojirimycin, and syringic acid. Hence, based on our findings, it can be concluded that M. alba leaves can be consumed as a promising dietary supplement and can be formulated as phytopharmaceutical for the management of various metabolic disorders.

Development of Synergy-Based Combination of Methanolic Extract of Andrographis paniculata and Berberis aristata Against E. coli and S. aureus.

This study evaluates the antibacterial activity and phytochemical characterizations of Andrographis paniculata extract (APE) and Berberis aristata extract (BAE). The stem of Andrographis paniculata (AP) and root of Berberis aristata (BA) were extracted with methanol. The results confirmed that APE and BAE possess high phenolic and flavonoid content. The antioxidant activity of the APE and BAE showed an elevated potential to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals with IC50 of 95.03 µg/mL and 256.26 µg/mL, respectively. A total of 35 and 32 metabolites in APE and BAE, respectively, were identified through mass spectrometry analysis, whereas 17 and 12 metabolites in APE and BAE, respectively, were detected through high-performance thin-layer chromatography (HPTLC) fingerprinting profiling. Antibacterial activity of the extracts was performed by the well diffusion and microdilution method, and the findings showed that APE and BAE had antibacterial activities against E. coli and S. aureus. The growth curve and time-kill study showed that the extracts had a bacteriostatic effect. A combination study with the standard drug was carried out using the microdilution checkerboard method in which most of the combinations showed synergistic interactions. The findings of this study have shown that APE and BAE are good sources of antibacterial compounds and can be used for treating infectious diseases caused by E. coli and S. aureus.

Receptor-Mediated Targeting in Breast Cancer through Solid Lipid Nanoparticles and Its Mechanism.

Nanoparticles have gained prominence in many areas and domains worldwide, such as metallic NP, carbon dots, quantum dots, polymeric NP, nano-suspension, nanocrystals, solid lipid nanoparticles (SLN), etc. and have been applied in the field of medicine as nanomedicine with promising results. Rise in cancer mortality rate has been an issue for a long time with female breast cancer as one of the most detected cancers. No permanent treatment has been developed till date could combat breast cancer with minimum side effects that are not long-lasting as there is no proper technique through which the anticancer drugs can recognize benign or malignant or normal cells that causes systematic toxicity. Advancement in technology has led to the discovery of many biological pathways and mechanisms. Tumor cells or cancer cells overexpress some high-affinity receptors that can be targeted to deliver the anticancer drugs at specific site using these pathways and mechanisms. Solid lipid nanoparticles (SLN) are among some of the excellent drug delivery systems, especially stealth SLN (sSLN). SLN, when conjugated with a ligand (called as sSLN), has affinity and specificity towards a specific receptor, and can deliver the drug in breast cancer cells overexpressing the receptors. Using this technique, various investigations have reported better anti-breast cancer activity than simple SLN (non-conjugated to ligand or no receptor targeting). This review includes the investigations and data on receptor-mediated targeting in breast cancer from 2010 to 2021 by searching different databases. Overall, information on SLN in different cancers is reviewed. In vivo investigations, pharmacokinetics, biodistribution, and stability are discussed to describe the efficacy of sSLN. Investigations included in this review demonstrate that sSLN delivers the drug by overcoming the biological barriers and shows enhanced and better activity than non-conjugated SLN which also verifies that a lesser concentration of drug can show anti-breast cancer activity. The efficacy of medicines could be increased with lower cancer deaths through stealth-SLN. Due to the low cost of synthesis, biocompatibility and easy to formulate, more study is needed in vitro and in vivo so that this novel technique could be utilized in the treatment of human breast cancer.

Synergy based Extracts of Medicinal Plants: Future Antimicrobials to Combat Multidrug Resistance.

The use of herbal medicines and supplements in the last thirty years has increased enormously. Herbal medication has demonstrated promising and effective potential against various diseases. Herbal and phytoconstituent medications are gaining popularity globally and many people are adopting herbal remedies to deal with different health issues. The indiscriminate use of antibiotics, due to the development of antimicrobial resistance, poses an unprecedented problem for human civilization. Bacterial infections are difficult to cure because of the propensity of microbes to acquire resistance to a wide range of antimicrobial drugs. New compounds are being explored and quantified for possible antibacterial activity with little or no side effects. Researchers are investigating the range of therapeutic plants mentioned in Unani, Ayurveda, and Siddha around the globe. Known and commonly acclaimed global databases such as PubMed, Research Gate, Science Direct, Google Scholar were searched using different search strings such as Indian medicinal plants, multidrug resistance (MDR), thin layer chromatography (TLC), antimicrobials, and Synergism were used in diverse combinations to reclaim numerous citations associated with this area. Thus, the current review aims to shed a light on the information of medicinal plants as a potential foundation of herbal drugs and elucidate how synergism and TLC bioautography play a crucial role in finding antimicrobial compounds.