National Institute of Pharmaceutical Education and Research, Kolkata

OBJECTIVE The objective of this study is to investigate the neuroprotective effects of β-sitosterol using the AlCl3 model of Alzheimer's Disease. Background Cognitive impairment can result from a variety of causes outside of merely neurological disorders. Exposure to toxins, depression, metabolic diseases, and brain injury are some factors that might impair cognition. There is a lot of research being done on how to treat memory loss using different medications, and for this particular study, we have selected sitosterol. C57BL/6 mice were subjected to an AlCl3-induced paradigm to study cognitive decline and behavioural abnormalities. In the AlCl3 cognition deficit mouse model, this study looked into the possibility of beta-sitosterol to improve cognition. 24 mice were randomly divided into 4 groups (1-4), each receiving one of the following treatments: distilled water for group 1, AlCl3 for group 2, AlCl3 + -sitosterol for group 3, and -sitosterol for group 4. After three-week research, neurobehavioral variables such as cognition and spatial learning were assessed. Congo red staining of beta-amyloid was used to assess immunohistochemical expression in the brain. The investigation is further supported by biochemical estimates of acetylcholinesterase, acetylcholine, and GSH. According to this study, β-sitosterol was effective in reducing the AlCl3 model's deficiencies in spatial learning and memory. METHODS AlCl3 model was used to study cognition decline and behavioral impairments in C57BL/6 mice. Animals were randomly assigned into 4 groups with the following treatments: Group 1 received normal saline for 21 days, Group 2 received AlCl3 (10mg/kg) for 14 days; Group 3 received AlCl3(10mg/kg) for 14 days + β-sitosterol (25mg/kg) for 21 days; while Group 4 was administered β-sitosterol (25mg/kg) for 21 days. On day 22, we performed the behavioral studies using a Y maze, passive avoidance test, and novel object recognition test for all groups. Then the mice were sacrificed. The corticohippocampal region of the brain was isolated for acetylcholinesterase (AChE), acetylcholine (ACh), and GSH estimation. We conducted histopathological studies using Congo red staining to measure β -amyloid deposition in the cortex and hippocampal region for all animal groups. Objective To investigate the neuroprotective effects of β-sitosterol using the AlCl3 model of Alzheimer's Disease RESULTS AlCl3 successfully induced cognitive decline in mice following a 14-day induction period, as shown by significantly decreased (p<0.001) in step-through latency, % alterations, and preference index values. These animals also exhibited a substantial decrease in ACh (p <0.001) and GSH (p<0.001) and a rise in AChE (p<0.001) compared to the control group. Mice administered with AlCl3 and β-sitosterol showed significantly higher step-through latency time, % alteration time, and % preference index (p<0.001) and higher levels of ACh, GSH, and lower levels of AChE in comparison to the AlCl3 model. AlCl3-administered animals also showed higher β -amyloid deposition, significantly reduced in the β-sitosterol treated group. Method AlCl3 model was used to study cognition decline and behavioral impairments in C57BL/6 mice. Animals were randomly assigned into 4 groups with the following treatments: group 1 received normal saline for 21 days, group 2 received AlCl3(10mg/kg) for 14 days; Group 3 received AlCl3(10mg/kg) for 14 days + β-sitosterol (25mg/kg) for 21 days; while Group 4 was administered β-sitosterol (25mg/kg) for 21 days. On day 22, we performed the behavioral studies using a Y maze, passive avoidance test, and novel object recognition test for all groups. Then the mice were sacrificed. The corticohippocampal region of the brain was isolated for acetylcholinesterase, acetylcholine, and GSH estimation. We conducted histopathological studies using Congo red staining to measure β -amyloid deposition in the cortex and hippocampal region for all animal groups. CONCLUSION AlCl3 was effectively employed to induce a cognitive deficit in mice, resulting in neurochemical changes and cognitive decline. β-sitosterol treatment mitigated AlCl3-mediated cognitive impairment Result AlCl3 successfully induced cognitive decline in mice following a 14-day induction period, as shown by significantly decreased (p<0.001) in step-through latency, % alterations, and preference index values. These animals also exhibited a substantial decrease in Ach (p <0.001) and GSH (p<0.001) and a rise in AChE (p<0.001) compared to the control group. Mice administered with AlCl3 and β-sitosterol showed significantly higher step-through latency time, % alteration time, and % preference index (p<0.001) and higher levels of Ach, GSH, and lower levels of AchE in comparison to the AlCl3 model. AlCl3-administered animals also showed higher β -amyloid deposition, significantly reduced in the β-sitosterol treated group. Other na

Background 2-pyridone is frequently used to synthesize and develop new bioactive molecules approved for treating many diseases. The produced compounds play a significant role in inhibiting cancer growth. Background : 2-pyridone is frequently used to synthesize and develop new bioactive molecules that have been approved for use in the treatment of many diseases, and the produced compounds play a significant role in the inhibition of cancer growth Objectives Through a molecular docking investigation, we determined the binding affinity of 2-pyridone compounds with the Matrix Metalloproteinase receptor, which allowed us to develop, produce, and test the in vitro anticancer efficacy of those compounds. Objective Through a molecular docking investigation, we were able to determine the binding affinity of 2-pyridone compounds with the Matrix Metalloproteinase receptor, which allowed us to develop, produce, and test the in-vitro anticancer efficacy of those compounds Method 2-pyridones (A1-A12) were synthesized in a multistep process, followed by spectrum analysis to confirm the structure. In-silico screening of the synthesized compounds was carried out with the assistance of AutoDock software. Flow cytometry was used on the HT-29 colon cancer cell line to measure A1-A12’s anticancer effect in a lab setting. Method 2-pyridones (A1-A12) were synthesized in a multistep process, followed by their spectrum analysis for confirmation of the structure. In-silico screening of the synthesized compounds was carried out with the assistance of autodock software. Flow cytometry was used on the HT-29 colon cancer cell line to measure A1-A12's anticancer effect in a lab setting Results The enzyme matrix metalloproteinase receptor and A1-A12 interacted unexpectedly during a docking study (MMP3, MMP9 & MMP13). Research has shown a strong affinity for MMP3 receptors for A9, A10, A11, A12, and A4, respectively. Further flow cytometric testing revealed compound A9 (R1) to be highly cytotoxic, with an IC50 value of 20.77 M. The anticancer activity of A9 (R1) against HT-29 colon cancer cell lines was also confirmed by in vitro results. Result The enzyme matrix metalloproteinase receptor and A1-A12 appeared to interact in an unexpected way during a docking study (MMP3, MMP9 & MMP13). Research has shown a strong affinity for MMP3 receptors for A9, A10, A11, A12, and A4, respectively. Further flow cytometric testing revealed compound A9 (R1) to be highly cytotoxic, with an IC50 value of 20.77 M. The anticancer activity of A9 (R1) against HT-29 colon cancer cell lines was also confirmed by in-vitro results. Conclusion These findings suggested that 2-pyridone compounds have promising therapeutic potential for cancer treatment, and more research on these lead moieties would be advantageous to discovering an effective anticancer drug. Conclusion These findings suggested that 2-pyridone compounds have promising therapeutic potentials for the treatment of cancer, and more research on these lead moieties would be advantageous to the process of discovering an effective anticancer drug.

The outbreak of the COVID-19 propagates, pressurizing the healthcare system by emphasizing and worsening the inequities. While many vaccines have shown excellent efficacy in protecting the general public from the COVID-19 infection, the efficacy of these vaccines for people living with HIV (PLHIV), especially those having a different range of CD4 + T-cell, has yet to be thoroughly investigated. Few studies have uncovered the escalated infection and death rates due to the COVID-19 infection in individuals with low CD4 + T-cells. Additionally, PLHIV has a low CD4 + count; furthermore, specific CD4 + T cells for coronavirus have a vigorous Th1 role and are related to the protective antibody responses. Follicular helper T cells (TFH) are vulnerable to HIV and virus-specific CD4 & CD8 T-cells which are essential for viral infection clearance and defective immune responses which further contributes to the development of illness. The specific CD8 & CD4 + T-cell reaction to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) was identified in almost all COVID-19 recovered individuals, which is related to the size of antibodies of immunoglobulin G. It has previously been demonstrated that PLHIV has decreased responses to certain vaccines and that these responses are reliant on CD4 + T-cell levels. COVID-19 vaccines will likely have a lower response or limited effect, in PLHIV having low CD4 + T-cells.

Islamic literature has indicated that daily consumption of Ajwa dates heals a variety of chronic diseases and disorders. The current research investigates the neuroprotective effect of methanolic Ajwa seed extract (MASE) on lipopolysaccharide (LPS)-induced cognitive deficits using multiple approaches. For animal studies, MASE (200 and 400 mg/kg, p.o.) was administrated for thirty consecutive days, and four doses of LPS (250 µg/kg, i.p.) were injected to induce neurotoxicity. Memory functions were evaluated using elevated plus-maze and novel object recognition tests. Acetylcholine (ACh) and neuroinflammatory markers (cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-β1) were estimated in brain tissues. Studies of molecular docking and dynamics were conducted to provide insight into the molecular-level mechanisms. MASE administration resulted in a significant reversal of LPS-induced memory impairment in both maze models. Both doses of MASE elevated the ACh levels in an LPS-treated rat brain. In addition, the extract lowered COX-2 and proinflammatory cytokines (TNF-α and IL-6) while increasing anti-inflammatory cytokines (IL-10 and TGF-β1) in LPS-treated brain tissues. Molecular modeling results revealed that the compound’s ellagic acid, epicatechin, catechin, kaempferol, quercetin, and apigenin have the potential to act as a dual inhibitor of acetylcholinesterase (AChE) and COX-2 and can be responsible for the improvement of both cholinergic and inflammatory conditions, while the cinnamic acid, hesperidin, hesperetin, narengin, and rutin compounds are responsible only for the improvement of cholinergic transmission. The above compounds acted by interacting with the key residues Trp84, Asp72, Gly118, Ser200, Tyr334, and His440, which are responsible for the hydrolysis of ACh in AChE, while the COX-2 is inhibited by interacting with the residues (Val349, Leu352, Tyr355, Tyr385, Ala527, Ser530, and Leu531) of the hydrophobic channel. By promoting cholinergic activity and protecting neuroinflammation in the rat brain, MASE provides neuroprotection against LPS-induced cognitive deficits. Our preliminary findings will help with further drug discovery processes related to neuroinflammation-related neurodegeneration.

The misfolding of amyloid beta (Aβ) peptides into Aβ fibrillary aggregates is a major hallmark of Alzheimer's disease (AD), which responsible for the excess production of hydrogen peroxide (H2O2), a prominent reactive oxygen species (ROS) from the molecular oxygen (O2) by the reduction of the Aβ-Cu(I) complex. The excessive production of H2O2 causes oxidative stress and inflammation in the AD brain. Here, we have designed and developed a dual functionalized molecule VBD by using π-conjugation (C═C) in the backbone structure. In the presence of H2O2, the VBD can turn into fluorescent probe VBD-1 by cleaving of the selective boronate ester group. The fluorescent probe VBD-1 can undergo intramolecular charge transfer transition (ICT) by a π-conjugative system, and as a result, its emission increases from the yellow (532 nm) to red (590 nm) region. The fluorescence intensity of VBD-1 increases by 3.5-fold upon binding with Aβ fibrillary aggregates with a high affinity (Kd = 143 ± 12 nM). Finally, the VBD reduces the cellular toxic H2O2 as proven by the CCA assay and DCFDA assay and the binding affinity of VBD-1 was confirmed by using in vitro histological staining in 8- and 18-month-old triple transgenic AD (3xTg-AD) mice brain slices.

Dengue is a vector borne viral disease caused by a Flavivirus whereas the COVID‐19 pandemic was caused by a highly contagious virus, SARS‐CoV‐2 belonging to family Coronaviridae. However, COVID‐19 severity was observably less in dengue endemic countries and vice versa especially during the active years of the pandemic (2019‐2021). We observed that dengue virus (DENV) antibodies (Abs) could cross‐react with SARS‐CoV‐2 spike antigen. This resulted in SARS‐CoV‐2 false positivity by rapid Ab test kits. DENV Abs binding to SARS‐CoV‐2 receptor binding domain (and the reverse scenario), as revealed by docking studies further validated DENV and SARS‐CoV‐2 cross‐reactivity. Finally, SARS‐CoV‐2 Abs were found to cross‐neutralize DENV1 and DENV2 in virus neutralization test (VNT). Abs to other pathogens like Plasmodium, were also cross‐reactive but non‐neutralizing for SARS‐CoV‐2. Here, we analyse the existing data on SARS‐CoV‐2 cross‐reactivity with other pathogens, especially dengue to assess its impact on health (cross‐protection?) and differential sero‐diagnosis/surveillance. This article is protected by copyright. All rights reserved.

Tautomerism is an important phenomenon exhibited by many drugs. As we discuss in this review, identifying the different tautomers of drugs and exploring their importance in the mechanisms of drug action are integral components of current drug discovery. Nuclear magnetic resonance (NMR), infrared (IR), ultraviolet (UV), Raman, and terahertz spectroscopic techniques, as well as X-ray diffraction, are useful for exploring drug tautomerism. Quantum chemical methods, in association with pharmacoinformatics tools, are being used to evaluate tautomeric preferences in terms of energy effects. Desmotropy (i.e., tautomeric polymorphism) of the drugs is particularly important in drug delivery studies.

During the last two decades, yeast has been used as a biological tool to produce various small molecules, biofuels, etc., using an inexpensive bioprocess. The application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated protein (Cas) techniques in yeast genetic and metabolic engineering has made a paradigm shift, particularly with a significant improvement in targeted chromosomal integration using synthetic donor constructs, which was previously a challenge. This study reports the CRISPR-Cas9-based highly efficient strategy for targeted chromosomal integration and in-frame expression of a foreign gene in the genome of Saccharomyces cerevisiae (S. cerevisiae) by homology-dependent recombination (HDR); our optimized methods show that CRISPR-Cas9-based chromosomal targeted integration of small constructs at multiple target sites of the yeast genome can be achieved with an efficiency of 74%. Our study also suggests that 15 bp microhomology flanked arms are sufficient for 50% targeted knock-in at minimal knock-in construct concentration. Whole-genome sequencing confirmed that there is no off-target effect. This study provides a comprehensive and streamlined protocol that will support the targeted integration of essential genes into the yeast genome for synthetic biology and other industrial purposes. Highlights • CRISPR-Cas9 based in-frame expression of foreign protein in Saccharomyces cerevisiae using Homology arm without a promoter. • As low as 15 base pairs of microhomology (HDR) are sufficient for targeted integration in Saccharomyces cerevisiae. • The methodology is highly efficient and very specific as no off-targeted effects were shown by the whole-genome sequence.

The DNA templated bio‐orthogonal synthesis of macrocyclic gene modulators is illustrated in the cover picture accompanying the Research Article (DOI: 10.1002/anie.202215245) by Jyotirmayee Dash and co‐workers. DNA secondary structures present in the telomere and oncogene promoter proximally orient bi‐functional alkyne and azide fragments, enabling bond formation via Cu‐free azide–alkyne cycloaddition in live cells. The high‐affinity DNA binding macrocyclic ligand efficiently suppresses oncogene expression in cancer cells.

The DNA templated bio‐orthogonal synthesis of macrocyclic gene modulators is illustrated in the cover picture accompanying the Research Article (DOI: 10.1002/ange.202215245) by Jyotirmayee Dash and co‐workers. DNA secondary structures present in the telomere and oncogene promoter proximally orient bi‐functional alkyne and azide fragments, enabling bond formation via Cu‐free azide–alkyne cycloaddition in live cells. The high‐affinity DNA binding macrocyclic ligand efficiently suppresses oncogene expression in cancer cells.

The surgical needle insertion process is widely applied in medical interference. During the insertion process, the inhomogeneity and denseness of the soft tissues make it tough to detect the essential tissue damage, a rupture occurs that contains huge forces and material deformations. This study is very important, as all the above-mentioned factors are very significant for modern invasive surgery so that the success rate of the surgery can increase and the patient recovers smoothly. This investigation intends to perform minimally invasive surgical (MIS) procedures and reduce the living tissue damage while performing the biopsy, PCNL, etc. The force model was calculated by needle insertion experimentally, and also estimated the needle tip geometry, and diameter influences the fracture toughness. Validate exp. results with simulation results and other papers. During the rotational needle insertion process, the winds-up of the gel occurs and the diameter of the hole was increasing with increased rpm.

Toehold switches are de novo designed riboregulators that contain two RNA components interacting through linear‐linear RNA interactions, regulating the gene expression. These are highly versatile, exhibit excellent orthogonality, wide dynamic range, and are highly programmable, so can be used for various applications in synthetic biology. In this review, we summarized and discussed the design characteristics and benefits of toehold switch riboregulators over conventional riboregulators. We also discussed applications and recent advancements of toehold switch riboregulators in various fields like gene editing, DNA nanotechnology, translational repression, and diagnostics (detection of microRNAs and some pathogens). Toehold switches, therefore, furnished advancement in the applications of synthetic biology in various fields by concealing drawbacks with their prominent features. This article is protected by copyright. All rights reserved.

The delivery of drugs via transdermal routes is an attractive approach due to ease of administration, bypassing of the first-pass metabolism, and the large skin surface area. However, a major drawback is an inability to surmount the skin’s stratum corneum (SC) layer. Therefore, techniques reversibly modifying the stratum corneum have been a classical approach. Surmounting the significant barrier properties of the skin in a well-organised, momentary, and harmless approach is still challenging. Chemical permeation enhancers (CPEs) with higher activity are associated with certain side effects restricting their advancement in transdermal drug delivery. Furthermore, complexity in the interaction of CPEs with the skin has led to difficulty in elucidating the mechanism of action. Nevertheless, CPEs-aided transdermal drug delivery will accomplish its full potential due to advancements in analytical techniques, synthetic chemistry, and combinatorial studies. This review focused on techniques such as drug–vehicle interaction, vesicles and their analogues, and novel CPEs such as lipid synthesis inhibitors (LSIs), cell-penetrating peptides (CPPs), and ionic liquids (ILs). In addition, different types of microneedles, including 3D-printed microneedles, have been focused on in this review.

A series of uncharged salicylaldehyde oximes were synthesized and evaluated for the reactivation of organophosphorus (OP) nerve agents simulants Diethylchlorophosphonate (DCP) & Diethylcyanophosphonate (DCNP) and pesticides (paraoxon & malaoxon) inhibited electric eel Acetylcholinesterase (AChE). The computational software Swiss ADME and molinspiration were used to unfold the probability of drug-likeness properties of the oximes derivatives. Substituted aromatic oximes with diethylamino or bromo group with free hydroxyl group ortho to oxime moiety were found efficient to regenerate the enzymatic activity in in-vitro AChE assay. The alkylation of the ortho hydroxyl group of derivatives led to the loss of reactivation potential. The derivatives with a hydroxyl group and without oxime group and vice versa did not show significant reactivation potency against tested OP toxicants. Further, we also evaluated the reactivation potential of these selected molecules on the rat brain homogenate against different OPs inhibited ChE and found maximum reactivation potency of oxime 2e. The in-vitro results were further validated by molecular docking and dynamic studies which showed that the hydroxyl group interacted with serine amino acids in the catalytic anionic site of AChE enzyme and was stable up to 200 ns consequently providing proper orientation to oxime moiety for reactivating the OP inhibited enzyme. It has thus been proved by the structure-activity relationship of oximes derivatives that hydroxyl group ortho to oxime is essential for reactivating OP inhibited electric eel AChE. Amongst the twenty-one oximes derivatives, 2e was found to be most active in regenerating the paraoxon, malaoxon, DCP and DCNP inhibited AChE enzyme.

Background Constipation is one of the most frequent abnormalities of the gastrointestinal system that affects the patient’s quality of life. Constipation is more common in women and affects them more frequently as they get older. Many constipated patients take over-the-counter drugs for treatment, but some do not respond to these medicines and need newer, more expensive drugs. Still, many patients are not completely satisfied with these medicines. Unlike other areas, constipation research is not given much importance. Objective This review discusses targets such as ClC-2, CFTR, opioid receptors, and 5HT-4 receptors, which are important in constipation therapy. The recent focus is also on the gut microbiome with the help of various randomized controlled trials. Pharmacological advances have also added novel targets such as IBAT, PAR-2, and intestinal NHE-3 for constipation treatment. Methods This review summarises the research on these targets collected from various databases. ClC-2 and CFTR are involved in intestinal chloride secretion followed by sodium or water, which increases stool passage. Non-cancer pain treatment with opioids targeting opiate receptors is considered in 40–90% of patients, which causes constipation as a side effect. On activation, 5HT-4 receptors increase gastrointestinal motility. IBAT is responsible for transporting bile acid into the liver. Bile acid will reach the colon by inhibiting IBAT, stimulating colonic motility, and providing a laxative effect. Activation of the ghrelin receptor results in prokinetic activity in both animals and humans. Intestinal NHE-3 mediates the absorption of Na+ and the secretion of hydrogen into the intestine. Many reports show that PAR-2 is involved in the pathogenesis of gastrointestinal diseases. The gut microbiota influences the peristaltic action of the intestine. Conclusion Drugs working on these targets positively impact the treatment of constipation, as do the drugs that are currently in clinical trials acting on these targets. The results from the ongoing clinical trials will also provide some valuable information regarding whether these medications will meet the patients’ needs in the future.

Proper regulation of cellular protein quality control is crucial for cellular health. It appears that the protein quality control machinery is subjected to distinct regulation in different cellular contexts such as in somatic cells and in germ cells. Heat shock factors (HSFs) play critical role in the control of quality of cellular proteins through controlling expression of many genes encoding different proteins including those for inducible protein chaperones. Mammalian cells exert distinct mechanism of cellular functions through maintenance of tissue-specific HSFs. Here, we have discussed different HSFs and their functions including those during spermatogenesis. We have also discussed the different heat shock proteins induced by the HSFs and their activities in those contexts. We have also identified several small molecule activators and inhibitors of HSFs from different sources reported so far.

A julolidine‐coupled benzoxazole‐based fluorescent chemosensor (BPOZ) is designed and developed to investigate the different target analyte interactions spectroscopically. Based on the ′off‐on‐off′ photoluminescence mechanism, the as‐prepared BPOZ is used for sequentially detecting Zn2+ and HSO4− ions, respectively. The UV‐visible absorption and photoluminescence spectral behavior is intramolecular charge transfer (ICT) in nature. When Zn2+ ions bind with BPOZ, its fluorescence is significantly enhanced at 512 nm due to chelation‐enhanced fluorescence. A green color emission is also visible under 365 nm UV light exposure, which is also confirmed by the color chromaticity diagram. Chelation‐enhanced photoluminescence is also manifested in the lifetime decay analysis. Further, it is well supported by different spectroscopic techniques and DFT analysis. In the presence of HSO4− ions, photoluminescence of the Zn2+ chelated BPOZ complex is significantly reduced, rebirthing the free BPOZ. The detection limit of BPOZ for Zn2+ and Zn2+ chelated BPOZ complex towards detecting Zn2+ and HSO4− ions is established to be in the order of nM and μM range, respectively, in the solution phase. Among the various explosive nitroaromatic compounds, picric acid (PA) quenched the emission of the Zn2+ chelated BPOZ complex, and the quenching mechanism is found to be both static and dynamic in nature. Using these chemically prearranged inputs and optical outputs, two inputs, INHIBIT, and three inputs, combinational logic gates have been constructed. The BPOZ chemosensor and Zn2+ chelated BPOZ complex are also employed to map Zn2+ ions and PA in the living cell. The performance of the BPOZ chemosensor and Zn2+ chelated BPOZ complex toward Zn2+ ions and PA proved that it could be exploited as a signal tool for environmental and biological samples. A julolidine‐coupled benzoxazole‐based dyad (BPOZ) is designed and developed to investigate the different target analyte interactions spectroscopically. The details photophysics of BPOZ is studied and employed for the cascade detection of Zn2+ and HSO4− ions or Zn2+ and picric acid (PA), respectively, based on the ‘off‐on‐off’ photoluminescence mechanism.

Background Non-alcoholic fatty liver disease (NAFLD) is now the most common form of chronic liver disease in the world, and it’s linked to a slew of other risk factors including diabetes, obesity, dysbiosis and inflammatory bowel disease. More than 30 years ago, a patient was diagnosed with fatty liver with excessive fat accumulation in hepatocytes, a disorder known as hepatosteatosis. There will be no promising therapeutic medicines available from 1980 to 2021 which can reverse the fatty liver to normal liver state. In this review, we highlighted on lipid droplet associated protein which play a major role in accumulation of fat in liver cells and how these cellular pathway could be a promising therapeutic approach to treat the fatty liver disease. Main body Over the last few decades, Western countries follow a high-fat diet and change their lifestyle pattern due to certain metabolic disorders prevalence rate is very high all over the world. NAFLD is a major health issue and burden globally nowadays. Researchers are trying to find out the potential therapeutic target to combat the disease. The exact pathophysiology of the disease is still unclear. In the present decades. There is no Food and Drug Administration approved drugs are available to reverse the chronic condition of the disease. Based on literature survey, lipid droplets and their associated protein like perilipins play an eminent role in body fat regulation. In this review, we explain all types of perilipins such as perilipin1-5 (PLIN1-5) and their role in the pathogenesis of fatty liver which will be helpful to find the novel pharmacological target to treat the fatty liver. Conclusion In this review, majorly focussed on how fat is get deposited into hepatocytes follow the cellular signalling involved during lipid droplet biogenesis and leads to NAFLD. However, up to date still there mechanism of action is unclear. In this review, we hypothesized that lipid droplets associated proteins like perilipins could be better pharmacological target to reverse the chronic stage of fatty liver disease and how these lipid droplets associated proteins hide a clue to maintain the normal lipid homeostasis in the human body.