Unraveling the interplay between globalization, financial development, economic growth, greenhouse gases, human capital, and renewable energy uptake in Indonesia: multiple econometric approaches.

Addressing global environmental concerns requires the widespread adoption of renewable energy sources. More research is needed to examine the relationships between renewable energy (RE) and globalization, economic growth, and environmental quality in Indonesia. Therefore, we examined how renewable energy usage in Indonesia has changed due to the dynamic effects of globalization, financial development, and environmental quality. Time-series data were analyzed using an autoregressive distributed lag (ARDL) model to test for cointegration and long-run/short-run dynamics between 1990 and 2020. In addition to ARDL bounds testing, we used the Johansen and Engle-Granger cointegration methods for confirmation. Globalization, financial progress, human capital, greenhouse gas emissions, and economic expansion have favorable long- and short-term effects on renewable energy sources. Globalization has enabled Indonesia to expand trade, FDI, and financial investment. It has also increased energy-efficient technology use due to environmental policies. The computed results are robust enough to substitute estimators, such as dynamic ordinary least squares (DOLS), fully modified least squares (FMOLS), and canonical cointegrating regression (CCR). We recommend the implementation of policies that support financial and environmental development by utilizing renewable resources and increasing investments in renewable energy ventures.

Potentials of curcumin against polycystic ovary syndrome: Pharmacological insights and therapeutic promises.

Polycystic ovary syndrome (PCOS) is a common hormonal disorder among women (4%-20%) when the ovaries create abnormally high levels of androgens, the male sex hormones that are typically present in women in trace amounts. The primary characteristics of PCOS include oxidative stress, inflammation, hyperglycemia, hyperlipidemia, hyperandrogenism, and insulin resistance. Generally, metformin, spironolactone, eflornithine and oral contraceptives are used to treat PCOS, despite their several side effects. Therefore, finding a potential candidate for treating PCOS is necessary. Curcumin is a major active natural polyphenolic compound derived from turmeric (Curcuma longa). A substantial number of studies have shown that curcumin has anti-inflammatory, anti-oxidative stress, antibacterial, and anti-apoptotic activities. In addition, curcumin reduces hyperglycemia, hyperlipidemia, hyperandrogenism, and insulin resistance in various conditions, including PCOS. The review highlighted the therapeutic aspects of curcumin against the pathophysiology of PCOS. We also offer a hypothesis to improve the development of medicines based on curcumin against PCOS.

Identification of Leading Compounds from Euphorbia neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies.

Coronavirus disease-19 (COVID-19) are deadly and infectious disease that impacts individuals in a variety of ways. Scientists have stepped up their attempts to find an antiviral drug that targets the spike protein (S) of Angiotensin converting enzyme 2 (ACE2) (receptor protein) as a viable therapeutic target for coronavirus. The most recent study examines the potential antagonistic effects of 17 phytochemicals present in the plant extraction of Euphorbia neriifolia on the anti-SARS-CoV-2 ACE2 protein. Computational techniques like molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) investigations, and molecular dynamics (MD) simulation analysis were used to investigate the actions of these phytochemicals. The results of molecular docking studies showed that the control ligand (2-acetamido-2-deoxy-ß-D-glucopyranose) had a binding potential of -6.2 kcal/mol, but the binding potentials of delphin, ß-amyrin, and tulipanin are greater at -10.4, 10.0, and -9.6 kcal/mol. To verify their drug-likeness, the discovered hits were put via Lipinski filters and ADMET analysis. According to MD simulations of the complex run for 100 numbers, delphin binds to the SARS-CoV-2 ACE2 receptor's active region with good stability. In root-mean-square deviation (RMSD) and root mean square fluctuation (RMSF) calculations, delphinan, ß-amyrin, and tulipanin showed reduced variance with the receptor binding domain subunit 1(RBD S1) ACE2 protein complex. The solvent accessible surface area (SASA), radius of gyration (Rg), molecular surface area (MolSA), and polar surface area (PSA) validation results for these three compounds were likewise encouraging. The convenient binding energies across the 100 numbers binding period were discovered by using molecular mechanics of generalized born and surface (MM/GBSA) to estimate the ligand-binding free energies to the protein receptor. All things considered, the information points to a greater likelihood of chemicals found in Euphorbia neriifolia binding to the SARS-CoV-2 ACE2 active site. To determine these lead compounds' anti-SARS-CoV-2 potential, in vitro and in vivo studies should be conducted. How to cite this article: Islam MN, Pramanik MEA, Hossain MA, et al. Identification of Leading Compounds from Euphorbia Neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies. Euroasian J Hepato-Gastroenterol 2023;13(2):89-107.

Protective Mechanisms of Nootropic Herb Shankhpushpi (Convolvulus pluricaulis) against Dementia: Network Pharmacology and Computational Approach.

Convolvulus pluricaulis (CP), a Medhya Rasayana (nootropic) herb, is a major ingredient in Ayurvedic and Traditional Chinese formulae indicated for neurological conditions, namely, dementia, anxiety, depression, insanity, and epilepsy. Experimental evidence suggests various neuroactive potentials of CP such as memory-enhancing, neuroprotective, and antiepileptic. However, precise mechanisms underlying the neuropharmacological effects of CP remain unclear. The study, therefore, aimed at deciphering the molecular basis of neuroprotective effects of CP phytochemicals against the pathology of dementia disorders such as Alzheimer's (AD) and Parkinson's (PD) disease. The study exploited bioinformatics tools and resources, such as Cytoscape, DAVID (Database for annotation, visualization, and integrated discovery), NetworkAnalyst, and KEGG (Kyoto Encyclopedia of Genes and Genomes) database to investigate the interaction between CP compounds and molecular targets. An in silico analysis was also employed to screen druglike compounds and validate some selective interactions. ADME (absorption, distribution, metabolism, and excretion) analysis predicted a total of five druglike phytochemicals from CP constituents, namely, scopoletin, 4-hydroxycinnamic acid, kaempferol, quercetin, and ayapanin. In network analysis, these compounds were found to interact with some molecular targets such as prostaglandin G/H synthase 1 and 2 (PTGS1 and PTGS2), endothelial nitric oxide synthase (NOS3), insulin receptor (INSR), heme oxygenase 1 (HMOX1), acetylcholinesterase (ACHE), peroxisome proliferator-activated receptor-gamma (PPARG), and monoamine oxidase A and B (MAOA and MAOB) that are associated with neuronal growth, survival, and activity. Docking simulation further confirmed interaction patterns and binding affinity of selected CP compounds with those molecular targets. Notably, scopoletin showed the highest binding affinity with PTGS1, NOS3, PPARG, ACHE, MAOA, MAOB, and TRKB, quercetin with PTGS2, 4-hydroxycinnamic acid with INSR, and ayapanin with HMOX1. The findings indicate that scopoletin, kaempferol, quercetin, 4-hydroxycinnamic acid, and ayapanin are the main active constituents of CP which might account for its memory enhancement and neuroprotective effects and that target proteins such as PTGS1, PTGS2, NOS3, PPARG, ACHE, MAOA, MAOB, INSR, HMOX1, and TRKB could be druggable targets against dementia.

Potential Therapeutic Implication of Herbal Medicine in Mitochondria-Mediated Oxidative Stress-Related Liver Diseases.

Mitochondria are double-membrane organelles that play a role in ATP synthesis, calcium homeostasis, oxidation-reduction status, apoptosis, and inflammation. Several human disorders have been linked to mitochondrial dysfunction. It has been found that traditional therapeutic herbs are effective on alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) which are leading causes of liver cirrhosis and hepatocellular carcinoma. The generation of reactive oxygen species (ROS) in response to oxidative stress is caused by mitochondrial dysfunction and is considered critical for treatment. The role of oxidative stress, lipid toxicity, and inflammation in NAFLD are well known. NAFLD is a chronic liver disease that commonly progresses to cirrhosis and chronic liver disease, and people with obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension are at a higher risk of developing NAFLD. NAFLD is associated with a number of pathological factors, including insulin resistance, lipid metabolic dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. As a result, the improvement in steatosis and inflammation is enough to entice researchers to look into liver disease treatment. However, antioxidant treatment has not been very effective for liver disease. Additionally, it has been suggested that the beneficial effects of herbal medicines on immunity and inflammation are governed by various mechanisms for lipid metabolism and inflammation control. This review provided a summary of research on herbal medicines for the therapeutic implementation of mitochondria-mediated ROS production in liver disease as well as clinical applications through herbal medicine. In addition, the pathophysiology of common liver disorders such as ALD and NAFLD would be investigated in the role that mitochondria play in the process to open new therapeutic avenues in the management of patients with liver disease.

Dietary carbohydrates: Pathogenesis and potential therapeutic targets to obesity-associated metabolic syndrome.

Metabolic syndrome (MetS) is a common feature in obesity, comprising a cluster of abnormalities including abdominal fat accumulation, hyperglycemia, hyperinsulinemia, dyslipidemia, and hypertension, leading to diabetes and cardiovascular diseases (CVD). Intake of carbohydrates (CHO), particularly a sugary diet that rapidly increases blood glucose, triglycerides, and blood pressure levels is the predominant determining factor of MetS. Complex CHO, on the other hand, are a stable source of energy taking a longer time to digest. In particular, resistant starch (RS) or soluble fiber is an excellent source of prebiotics, which alter the gut microbial composition, which in turn improves metabolic control. Altering maternal CHO intake during pregnancy may result in the child developing MetS. Furthermore, lifestyle factors such as physical inactivity in combination with dietary habits may synergistically influence gene expression by modulating genetic and epigenetic regulators transforming childhood obesity into adolescent metabolic disorders. This review summarizes the common pathophysiology of MetS in connection with the nature of CHO, intrauterine nutrition, genetic predisposition, lifestyle factors, and advanced treatment approaches; it also emphasizes how dietary CHO may act as a key element in the pathogenesis and future therapeutic targets of obesity and MetS.

Investigating the subsistence of Environmental Kuznets Curve in the midst of economic development, population, and energy consumption in Bangladesh: imminent of ARDL model.

The main purpose of this study is to analyze the existence of an environmental Kuznets curve (EKC) considering the midst of energy consumption, population and economic development. The main objective is to investigate the impact of energy consumption, population and economic development on CO2 emissions. This study has taken data from 1971 to 2020 to see the existence of an EKC in the country of Bangladesh. Besides population growth, energy consumption and economic development are also taken into consideration. An autoregressive distributed lag (ARDL) model was used to scrutinize cointegration based on selected variables and their respective I (0) and I (1) values. This study has confirmed the long-term existence of the EKC in the environment. The environmental Kuznets curve was also tested using economic performance coefficients on emissions. In the long run, EKC explains why per capita carbon output decreases with population expansion but turns down after a certain threshold level is achieved because of this inverted U-shaped pattern. For decades, increased energy consumption has been linked to worsening environmental conditions, according to this study. According to the findings, there are a wide variety of approaches to advancing Bangladesh's economy and improving its environmental quality. In the long run, the population has no positive impact on CO2 secretion. The use of fossil fuels such as gas and oil can have a detrimental environmental impact. As a result, if we want to conserve the environment, we need to use renewable energy sources like solar and biodiesel instead of traditional, nonrenewable fuels.

Protective effects of fucoidan against kidney diseases: Pharmacological insights and future perspectives.

Chronic kidney disease (CKD) is a major public health concern that costs millions of lives worldwide. Natural products are consistently being explored for the development of novel therapeutics in the management of CKD. Fucoidan is a sulfated polysaccharide predominantly extracted from brown seaweed, which has multiple pharmacological benefits against various kidney problems, including chronic renal failure and diabetic nephropathy. This review aimed at exploring literature to update the renoprotective effects of fucoidan, to get an understanding of pharmacological mechanisms, and to highlight the recent progress of fucoidan-based therapeutic development. Evidence shows that fucoidan is effective against inflammation, oxidative stress, and fibrosis in kidney. Fucoidan targets multiple signaling systems, including Nrf2/HO-1, NF-κB, ERK and p38 MAPK, TGF-ß1, SIRT1, and GLP-1R signaling that are known to be associated with CKD pathobiology. Despite these pharmacological prospects, the application of fucoidan is limited by its larger molecular size. Notably, low molecular weight fucoidan has shown therapeutic promise in some recent studies. However, future research is warranted to translate the outcome of preclinical studies into clinical use in kidney patients.

Empirical analysis of the feasible solution to mitigate the CO2 emission: evidence from Next-11 countries.

From the empirical findings, economic growth, energy consumption, fossil fuel use, and infrastructure all have a positive impact on CO2 emissions. Forest rent and industrialization show a mix of results to explain CO2 emissions in N-11 countries. Forest and agriculture have negative coefficients in most of the estimations which indicate the reduction of CO2 emissions in 11 countries. Through the evidence of variance decomposition (VD) analysis, this study found an inverted U-shaped EKC hypothesis in the long run. Moreover, through the econometric analysis, it is clear that forest area is important to reduce CO2 emissions in N-11 countries, where forest investment and planning would be effective for carbon reduction. Agricultural activities and production with green investment play an important role in mitigating CO2 emissions in N-11 countries.

Molecular pharmacology and therapeutic advances of the pentacyclic triterpene lupeol.

BACKGROUND: Plant triterpenoids are major sources of nutraceuticals that provide many health benefits to humans. Lupeol is one of the pentacyclic dietary triterpenoids commonly found in many fruits and vegetables, which is highly investigated for its pharmacological effect and benefit to human health. PURPOSE: This systematic review critically discussed the potential pharmacological benefits of lupeol and its derivatives as evidenced by various cellular and animal model studies. To gain insight into the pharmacological effects of lupeol, the network pharmacological approach is applied. Pharmacokinetics and recent developments in nanotechnology-based approaches to targeted delivery of lupeol along with its safety use are also discussed. METHODS: This study is dependent on the systematic and non-exhaustive literature survey for related research articles, papers, and books on the chemistry, pharmacological benefits, pharmacokinetics, and safety of lupeol published between 2011 and 2021. For online materials, the popular academic search engines viz. Google Scholar, PubMed, Science Direct, Scopus, ResearchGate, Springer, as well as official websites were explored with selected keywords. RESULTS: Lupeol has shown promising benefits in the management of cancer and many other human diseases such as diabetes, obesity, cardiovascular diseases, kidney and liver problems, skin diseases, and neurological disorders. The pharmacological effects of lupeol primarily rely on its capacity to revitalize the cellular antioxidant, anti-inflammatory and anti-apoptotic mechanisms. Network pharmacological approach revealed some prospective molecular targets and pathways and presented some significant information that could help explain the pharmacological effects of lupeol and its derivatives. Despite significant progress in molecular pharmacology, the clinical application of lupeol is limited due to poor bioavailability and insufficient knowledge on its mode of action. Structural modification and nanotechnology-guided targeted delivery of lupeol improve the bioavailability and bioactivity of lupeol. CONCLUSION: The pentacyclic triterpene lupeol possesses numerous human health-benefiting properties. This review updates current knowledge and critically discusses the pharmacological effects and potential applications of lupeol and its derivatives in human health and diseases. Future studies are needed to evaluate the efficacies of lupeol and its derivatives in the management and pathobiology of human diseases.

p53 Modulation of Autophagy Signaling in Cancer Therapies: Perspectives Mechanism and Therapeutic Targets.

The key tumor suppressor protein p53, additionally known as p53, represents an attractive target for the development and management of anti-cancer therapies. p53 has been implicated as a tumor suppressor protein that has multiple aspects of biological function comprising energy metabolism, cell cycle arrest, apoptosis, growth and differentiation, senescence, oxidative stress, angiogenesis, and cancer biology. Autophagy, a cellular self-defense system, is an evolutionarily conserved catabolic process involved in various physiological processes that maintain cellular homeostasis. Numerous studies have found that p53 modulates autophagy, although the relationship between p53 and autophagy is relatively complex and not well understood. Recently, several experimental studies have been reported that p53 can act both an inhibitor and an activator of autophagy which depend on its cellular localization as well as its mode of action. Emerging evidences have been suggested that the dual role of p53 which suppresses and stimulates autophagy in various cencer cells. It has been found that p53 suppression and activation are important to modulate autophagy for tumor promotion and cancer treatment. On the other hand, activation of autophagy by p53 has been recommended as a protective function of p53. Therefore, elucidation of the new functions of p53 and autophagy could contribute to the development of novel therapeutic approaches in cancer biology. However, the underlying molecular mechanisms of p53 and autophagy shows reciprocal functional interaction that is a major importance for cancer treatment and manegement. Additionally, several synthetic drugs and phytochemicals have been targeted to modulate p53 signaling via regulation of autophagy pathway in cancer cells. This review emphasizes the current perspectives and the role of p53 as the main regulator of autophagy-mediated novel therapeutic approaches against cancer treatment and managements.

Evaluation of in vitro and in silico anti-inflammatory potential of some selected medicinal plants of Bangladesh against cyclooxygenase-II enzyme.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants are sources of chemical treasures that can be used in treatment of different diseases, including inflammatory disorders. Traditionally, Heritiera littoralis, Ceriops decandra, Ligustrum sinense, and Polyscias scutellaria are used to treat pain, hepatitis, breast inflammation. The present research was designed to explore phytochemicals from the ethanol extracts of H. littoralis, C. decandra, L. sinense, and P. scutellaria to discern the possible pharmacophore (s) in the treatment of inflammatory disorders. MATERIAL AND METHODS: The chemical compounds of experimental plants were identified through GC-MS analysis. Furthermore, in-vitro anti-inflammatory activity was assessed in human erythrocytes and an in-silico study was appraised against COX-2. RESULTS: The experimental extracts totally revealed 77 compounds in GC-MS analysis and all the extracts showed anti-inflammatory activity in in-vitro assays. The most favorable phytochemicals as anti-inflammatory agents were selected via ADMET profiling and molecular docking with specific protein of the COX-2 enzyme. Molecular dynamics simulation (MDS) confirmed the stability of the selected natural compound at the binding site of the protein. Three phytochemicals exhibited the better competitive result than the conventional anti-inflammatory drug naproxen in molecular docking and MDS studies. CONCLUSION: Both experimental and computational studies have scientifically revealed the folklore uses of the experimental medicinal plants in inflammatory disorders. Overall, N-(2-hydroxycyclohexyl)-4-methylbenzenesulfonamide (PubChem CID: 575170); Benzeneethanamine, 2-fluoro-. beta., 3, 4-trihydroxy-N-isopropyl (PubChem CID: 547892); and 3,5-di-tert-butylphenol (PubChem CID: 70825) could be the potential leads for COX-2 inhibitor for further evaluation of drug-likeliness.

Phytochemicals as a Complement to Cancer Chemotherapy: Pharmacological Modulation of the Autophagy-Apoptosis Pathway.

Bioactive plant derived compounds are important for a wide range of therapeutic applications, and some display promising anticancer properties. Further evidence suggests that phytochemicals modulate autophagy and apoptosis, the two crucial cellular pathways involved in the underlying pathobiology of cancer development and regulation. Pharmacological targeting of autophagy and apoptosis signaling using phytochemicals therefore offers a promising strategy that is complementary to conventional cancer chemotherapy. In this review, we sought to highlight the molecular basis of the autophagic-apoptotic pathway to understand its implication in the pathobiology of cancer, and explore this fundamental cellular process as a druggable anticancer target. We also aimed to present recent advances and address the limitations faced in the therapeutic development of phytochemical-based anticancer drugs.

Analysis of plant-derived phytochemicals as anti-cancer agents targeting cyclin dependent kinase-2, human topoisomerase IIa and vascular endothelial growth factor receptor-2.

Cancer is caused by a variety of pathways, involving numerous types of enzymes. Among them three enzymes i.e. Cyclin-dependent kinase-2 (CDK-2), Human topoisomerase IIα, and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) are three of the most common enzymes that are involved in the cancer development. Although many chemical drugs are already available in the market for cancer treatment, plant sources are known to contain a wide variety of agents that are proved to possess potential anticancer activity. In this experiment, total thirty phytochemicals were analyzed against the mentioned three enzymes using different tools of bioinformatics and in silico biology like molecular docking study, drug likeness property experiment, ADME/T test, PASS prediction, and P450 site of metabolism prediction as well as DFT calculation to determine the three best ligands among them that have the capability to inhibit the mentioned enzymes. From the experiment, Epigallocatechin gallate was found to be the best ligand to inhibit CDK-2, Daidzein showed the best inhibitory activities towards the Human topoisomerase IIα, and Quercetin was predicted to be the best agent against VEGFR-2. They were also predicted to be quite safe and effective agents to treat cancer. However, more in vivo and in vitro analyses are required to finally confirm their safety and efficacy in this regard.

Potential Therapeutic Action of Autophagy in Gastric Cancer Managements: Novel Treatment Strategies and Pharmacological Interventions.

Gastric cancer (GC), second most leading cause of cancer-associated mortality globally, is the cancer of gastrointestinal tract in which malignant cells form in lining of the stomach, resulting in indigestion, pain, and stomach discomfort. Autophagy is an intracellular system in which misfolded, aggregated, and damaged proteins, as well as organelles, are degraded by the lysosomal pathway, and avoiding abnormal accumulation of huge quantities of harmful cellular constituents. However, the exact molecular mechanism of autophagy-mediated GC management has not been clearly elucidated. Here, we emphasized the role of autophagy in the modulation and development of GC transformation in addition to underlying the molecular mechanisms of autophagy-mediated regulation of GC. Accumulating evidences have revealed that targeting autophagy by small molecule activators or inhibitors has become one of the greatest auspicious approaches for GC managements. Particularly, it has been verified that phytochemicals play an important role in treatment as well as prevention of GC. However, use of combination therapies of autophagy modulators in order to overcome the drug resistance through GC treatment will provide novel opportunities to develop promising GC therapeutic approaches. In addition, investigations of the pathophysiological mechanism of GC with potential challenges are urgently needed, as well as limitations of the modulation of autophagy-mediated therapeutic strategies. Therefore, in this review, we would like to deliver an existing standard molecular treatment strategy focusing on the relationship between chemotherapeutic drugs and autophagy, which will help to improve the current treatments of GC patients.

Designing novel epitope-based polyvalent vaccines against herpes simplex virus-1 and 2 exploiting the immunoinformatics approach.

Herpes Simplex Virus (HSV) is a highly infectious virus that is responsible for various types of orofacial and genital infections. Two types of HSV exist i.e. HSV-1 and HSV-2, that are infecting millions of people around the world. However, no satisfactory treatment or counter-measure has yet been discovered to fight against the HSV infections. In this study, three possible polyvalent subunit vaccines against multiple strains of HSV-1 and HSV-2, targeting the envelope glycoproteins- E, B, and D, were designed using the tools of reverse vaccinology and immunoinformatics. The highly antigenic, non-allergenic, non-toxic, non-homolog (to the human proteome), and 100% conserved epitopes across the selected strains and species (eight epitopes from each of the CTL, HTL, and BCL epitope groups), were selected for vaccine construction. These designed vaccines are expected to be effective against the selected viral types simultaneously (as a polyvalent vaccine), without producing any unwanted adverse reaction within the body. Finally, from the three vaccine constructs, one best vaccine was determined by molecular docking analysis and thereafter, the MD simulation and immune simulation studies of the best vaccine construct also yielded satisfactory results, pointing towards quite good stability of the complex. Finally, in silico cloning was performed for analyzing the effective mass production strategy of the best vaccine construct. However, wet lab-based study should be conducted on the suggested vaccines for validating their potentiality, safety, and efficacy.Communicated by Ramaswamy H. Sarma.

Potential Therapeutic Role of Phytochemicals to Mitigate Mitochondrial Dysfunctions in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a decline in cognitive function and neuronal damage. Although the precise pathobiology of AD remains elusive, accumulating evidence suggests that mitochondrial dysfunction is one of the underlying causes of AD. Mutations in mitochondrial or nuclear DNA that encode mitochondrial components may cause mitochondrial dysfunction. In particular, the dysfunction of electron transport chain complexes, along with the interactions of mitochondrial pathological proteins are associated with mitochondrial dysfunction in AD. Mitochondrial dysfunction causes an imbalance in the production of reactive oxygen species, leading to oxidative stress (OS) and vice versa. Neuroinflammation is another potential contributory factor that induces mitochondrial dysfunction. Phytochemicals or other natural compounds have the potential to scavenge oxygen free radicals and enhance cellular antioxidant defense systems, thereby protecting against OS-mediated cellular damage. Phytochemicals can also modulate other cellular processes, including autophagy and mitochondrial biogenesis. Therefore, pharmacological intervention via neuroprotective phytochemicals can be a potential strategy to combat mitochondrial dysfunction as well as AD. This review focuses on the role of phytochemicals in mitigating mitochondrial dysfunction in the pathogenesis of AD.

Curcumin analogs as the inhibitors of TLR4 pathway in inflammation and their drug like potentialities: a computer-based study.

Toll-like receptor 4 (TLR4) pathway is one of the major pathways that mediate the inflammation in human body. There are different anti-inflammatory drugs available in the market which specifically act on different signaling proteins of TLR4 pathway but they do have few side effects and other limitations for intended use in human body. In this study, Curcumin and its different analogs have been analyzed as the inhibitors of signaling proteins, i.e. Cycloxygenase-2 (COX-2), inhibitor of kappaß kinase (IKK) and TANK binding kinase-1 (TBK-1) of TLR4 pathway using different computational tools. Initially, three compounds were selected for respective target based on free binding energy among which different compounds were reported to have better binding affinity than commercially available drug (control). Upon continuous computational exploration with induced fit docking (IFD), 6-Gingerol, Yakuchinone A and Yakuchinone B were identified as the best inhibitors of COX-2, IKK, and TBK-1 respectively. Then their drug-like potentialities were analyzed in different experiments where they were also predicted to perform well. Hopefully, this study will uphold the efforts of researchers to identify anti-inflammatory drugs from natural sources.