Rationally designed febuxostat-based hydroxamic acid and its pH-Responsive nanoformulation elicits anti-tumor activity.

Attempts to furnish antitumor structural templates that can prevent the occurrence of drug-induced hyperuricemia spurred us to generate xanthine oxidase inhibitor-based hydroxamic acids and anilides. Specifically, the design strategy involved the insertion of febuxostat (xanthine oxidase inhibitor) as a surface recognition part of the HDAC inhibitor pharmacophore model. Investigation outcomes revealed that hydroxamic acid 4 elicited remarkable antileukemic effects mediated via HDAC isoform inhibition. Delightfully, the adduct retained xanthine oxidase inhibitory activity, though xanthine oxidase inhibition was not the underlying mechanism of its cell growth inhibitory effects. Also, compound 4 demonstrated significant in-vivo anti-hyperuricemic (PO-induced hyperuricemia model) and antitumor activity in an HL-60 xenograft mice model. Compound 4 was conjugated with poly (ethylene glycol) poly(aspartic acid) block copolymer to furnish pH-responsive nanoparticles (NPs) in pursuit of circumventing its cytotoxicity towards the normal cell lines. SEM analysis revealed that NPs had uniform size distributions, while TEM analysis ascertained the spherical shape of NPs, indicating their ability to undergo self-assembly. HDAC inhibitor 4 was liberated from the matrix due to the polymeric nanoformulation's pH-responsiveness, and the NPs demonstrated selective cancer cell targeting ability.

Development of Mycobacterium tuberculosis Enoyl Acyl Reductase (InhA) Inhibitors: A Mini-Review.

This review article delves into the critical role of Enoyl acyl carrier protein Reductase (InhA; ENR), a vital enzyme in the NADH-dependent acyl carrier protein reductase family, emphasizing its significance in fatty acid synthesis and, more specifically, the biosynthesis of mycolic acid. The primary objective of this literature review is to elucidate diverse scaffolds and their developmental progression targeting InhA inhibition, thereby disrupting mycolic acid biosynthesis. Various scaffolds, including thiourea, piperazine, thiadiazole, triazole, quinazoline, benzamide, rhodanine, benzoxazole, and pyridine, have been systematically explored for their potential as InhA inhibitors. Noteworthy findings highlight thiadiazole and triazole derivatives, demonstrating promising IC50 values within the nanomolar concentration range. The review offers comprehensive insights into InhA's structure, structure-activity relationships, and a detailed overview of distinct scaffolds as effective inhibitors of InhA.

Germacrone: A Multi-targeting Sesquiterpene with Promising Anti-cancer and Chronic Disease Applications.

BACKGROUND: Germacrone, a naturally occurring active compound found in essential oils extracted from medicinal plants within the Zingiberaceae family, has garnered attention for its potential therapeutic applications. Extensive research has highlighted its multi-targeting capabilities, positioning it as a promising treatment for various chronic diseases, including cancer, cardiovascular conditions, and neurodegenerative disorders like Alzheimer's disease. OBJECTIVE: This review aims to provide a comprehensive overview of germacrone as a scaffold for developing multi-targeting drugs with therapeutic potential against a range of chronic disorders. The study delves into the molecular mechanisms that underlie the therapeutic effects of germacrone and explores its potential targets, including NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction. METHODS: A systematic review of literature databases was conducted to gather relevant studies on germacrone and its therapeutic applications. The molecular mechanisms and potential targets of germacrone were examined to elucidate its multi-targeting capabilities. RESULTS: Germacrone exhibits significant potential in the management of chronic diseases, with demonstrated effects on various cellular pathways. The review highlights its impact on NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction, showcasing its versatility in targeting multiple pathways associated with chronic conditions. Germacrone has emerged as a promising candidate for the treatment of diverse chronic diseases. The understanding of its multi-targeting capabilities, coupled with its natural origin, positions it as a valuable scaffold for developing therapeutics. CONCLUSION: The exploration of germacrone as a structural framework for multi-targeting drugs offers a potential avenue to enhance efficacy while minimizing potential side effects. Further research and clinical trials are warranted to validate the therapeutic potential of germacrone in diverse medical contexts.

Leveraging a rationally designed veliparib-based anilide eliciting anti-leukemic effects for the design of pH-responsive polymer nanoformulation.

Careful recruitment of the components of the HDAC inhibitory template culminated in veliparib-based anilide 8 that elicited remarkable cell growth inhibitory effects against HL-60 cell lines mediated via dual modulation of PARP [(IC50 (PARP1) = 0.02 nM) and IC50 (PARP2) = 1 nM)] and HDACs (IC50 value = 0.05, 0.147 and 0.393 µM (HDAC1, 2 and 3). Compound 8 downregulated the expression levels of signatory biomarkers of PARP and HDAC inhibition. Also, compound 8 arrested the cell cycle at the G0/G1 phase and induced autophagy. Polymer nanoformulation (mPEG-PCl copolymeric micelles loaded with compound 8) was prepared by the nanoprecipitation technique. The mPEG-PCL diblock copolymer was prepared by ring-opening polymerization method using stannous octoate as a catalyst. The morphology of the compound 8@mPEG-PCL was examined using TEM and the substance was determined to be monodispersed, spherical in form, and had an average diameter of 138 nm. The polymer nanoformulation manifested pH-sensitive behaviour as a greater release of compound 8 was observed at 6.2 pH as compared to 7.4 pH mimicking physiological settings. The aforementioned findings indicate that the acidic pH of the tumour microenvironment might stimulate the nanomedicine release which in turn can attenuate the off-target effects precedentially claimed to be associated with HDAC inhibitors.

Decoding Therapeutic Applications of Quercetin: Recent Advancements in Nanotechnological Strategies.

For centuries, people have used herbal medicine to treat a diversity of health complications and as a natural substance, they have a favourable effect on our health. Herbal ingredients can be utilized as lead molecules in the innovation and development of a new drug. Flavonoids are a class of chemical compounds with diverse phenolic structures, and they are found in a wide variety of foods, including fruits, vegetables, cereals, bark, roots, stems, flowers, tea, and wine. Quercetin is the most prevalent polyphenolic bioflavonoid or flavonoid. Quercetin is found in many food products and has demonstrated a wide range of pharmacological activities, including the treatment of allergies, ocular diseases, metabolic ailments, inflammatory illnesses, cardiovascular ailments and arthritis. Quercetin has attracted interest as an emerging pharmacophore with the potential to significantly advance research and the development of novel therapeutic medicines for a variety of diseases. Despite having a huge therapeutic potential, these flavonoids have unfavourable pharmacokinetic characteristics, low bioavailability, and poor solubility, limiting their application in therapeutics. The objective of the current study is to present a new update on the major therapeutic uses of quercetin and other types of nanocarriers that contain quercetin to treat various ailments.

Marine-derived Compounds: A Powerful Platform for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a debilitating form of dementia that primarily affects cholinergic neurons in the brain, significantly reducing an individual's capacity for learning and creative skills and ultimately resulting in an inability to carry out even basic daily tasks. As the elderly population is exponentially increasing, the disease has become a significant concern for society. Therefore, neuroprotective substances have garnered considerable interest in addressing this universal issue. Studies have shown that oxidative damage to neurons contributes to the pathophysiological processes underlying AD progression. In AD, tau phosphorylation and glutamate excitotoxicity may play essential roles, but no permanent cure for AD is available. The existing therapies only manage the early symptoms of AD and often come with numerous side effects and toxicities. To address these challenges, researchers have turned to nature and explored various sources such as plants, animals, and marine organisms. Many historic holy books from different cultures emphasize that adding marine compounds to the regular diet enhances brain function and mitigates its decline. Consequently, researchers have devoted significant time to identifying potentially active neuroprotective substances from marine sources. Marine-derived compounds are gaining recognition due to their abundant supply of diverse chemical compounds with biological and pharmacological potential and unique mechanisms of action. Several studies have reported that plants exhibit multitarget potential in treating AD. In light of this, the current study focuses on marine-derived components with excellent potential for treating this neurodegenerative disease.

Therapeutic Potential and Clinical Effectiveness of Quercetin: A Dietary Supplement.

Fruits and vegetables (like apples, citrus, grapes, onions, parsley, etc.) are the primary dietary sources of quercetin. In addition, isolated quercetin is also available on the market as a dietary supplement with a daily dose of up to 1000 mg/d. The objective of the present study is to explore the therapeutic potential and clinical efficacy of quercetin as a dietary supplement. The present paper highlights the safety parameters and clinical trial studies with several targets reviewed from the data available on PubMed, Science Direct, ClinicalTrails. gov, and from many reputed foundations. The results of the studies prove the unique position of quercetin in the treatment of various disorders and the possibility of using phytochemicals such as quercetin for an efficient cure. As evidenced by the numerous published reports on human interventions, it has been concluded that quercetin intake significantly improves disease conditions with minimal adverse effects.

Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer.

Structural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C-C bond formation was attempted in this study. The impact of substituents with varied electronic effects (phenyl ring, position 2 of the benzopyran scaffold) on the antitumor properties was also assessed. Resultantly, the efforts yielded a furyl arm bearing benzopyran possessing a 4-fluoro phenyl ring (position 2) (14) that manifested a magnificent antitumor profile against the Ishikawa cell lines mediated through dual inhibition of PARP and tubulin [(IC50 (PARP1) = 74 nM, IC50 (PARP2) = 109 nM) and tubulin (IC50 = 1.4 µM)]. Further investigations confirmed the ability of 14 to induce apoptosis as well as autophagy and cause cell cycle arrest at the G2/M phase. Overall, the outcome of the study culminated in a tractable dual PARP-tubulin inhibitor endowed with an impressive activity profile against endometrial cancer.

Evolving Advances in the Cosmetic Use of Probiotics and Postbiotics: Health, Regulatory and Marketing Aspects.

Ongoing development in cosmetics is increasingly making use of probiotics, which are defined as "live microorganisms with health-enhancing properties mediated through ingestion or topical application to the host". The observation that several bacterial strains augment normal processes of healthy tissue maintenance, particularly for the skin, has opened up new avenues for the use of bacterial strains in cosmetics. A principal feature of such "cosmeceuticals" is an application of increasing insight into the biochemical nature of the skin's normal microbial flora, also called its microbiome. The opportunity of manipulating the skin microbiome to address various skin disorders has revealed novel routes for treatment. The skin microbiome manipulation approaches to address various skin disorders include skin microbiome transplantation, skin bacteriotherapy, and prebiotic stimulation. Research in this field has revealed that medical outcome-targeted manipulation of skin microbiome bacterial strain makeup may significantly increase skin health and appearance. Commercial availability of probiotic skincare products is rapidly expanding worldwide due to satisfactory laboratory results and public perception of probiotics as being intrinsically more wholesome than other bioactive substances, such as synthetics. Major outcomes of probiotic use include a significant reduction in skin wrinkling, acne and other conditions adversely affecting skin appearance and healthy function. Moreover, probiotics may additionally promote normal skin hydration, resulting in a vibrant and lustrous appearance. Nevertheless, significant technical challenges remain for the full optimization of probiotics in cosmetic products. This article summarizes the evolving nature of this field and explores current probiotic research initiatives, along with regulatory aspects and significant challenges in the manufacturing of cosmetics in the context of market expansion for these products.

In silico docking based screening of constituents from Persian shallot as modulators of human glucokinase.

Purpose: Small molecule glucokinase (GK) modulators not only decrease fasting and basal plasma sugar contents but also progress glucose tolerance. The hydro-ethanolic extract of the Persian shallot (Allium hirtifolium Boiss.) decreased blood glucose, improved plasma insulin and amplified GK action. The present study was proposed to screen phytoconstituents from Persian shallot as human GK activators using in silico docking studies. Methods: A total of 91 phytoconstituents reported in Persian shallot (A. hirtifolium Boiss.) were assessed in silico for the prediction of drug-like properties and molecular docking investigations were carried out with human GK using AutoDock vina with the aim of exploring the binding interactions between the phytoconstituents and GK enzyme followed by in silico prediction of toxicity. Results: Almost all the phytoconstituents tested showed good pharmacokinetic parameters for oral bioavailability and drug-likeness. In the docking analysis, cinnamic acid, methyl 3,4,5-trimethoxy benzoate, quercetin, kaempferol, kaempferol 3-O-ß-D-glucopyranosyl-(1- > 4)-glucopyranoside, 5-hydroxy-methyl furfural, ethyl N-(O-anisyl) formimidate, 2-pyridinethione and ascorbic acid showed appreciable hydrogen bond and hydrophobic type interactions with the allosteric site residues of the GK enzyme. Conclusion: These screened phytoconstituents may serve as promising hit molecules for further development of clinically beneficial and safe allosteric activators of the human GK enzyme.

Hemorrhoid Disease: A Review on Treatment, Clinical Research and Patent Data.

BACKGROUND: Hemorrhoid disease (HD) is an anal-rectal ailment that is commonly painful or may be painless and causes rectal bleeding with or without prolapsing anal tissue. It is generally associated with bleeding, prolapse, pruritus, and discomfort, which results in a diminished quality of life and well-being. OBJECTIVE: To highlight the recent developments in terms of safety, clinical efficacy, and marketed formulation for the effective management of hemorrhoids. METHOD: Reported literature available on Scopus, PubMed, Science Direct, Clinicaltrails.gov, and from many reputed foundations has been studied to summarize the recent development and clinical studies for the management of hemorrhoids. RESULTS AND CONCLUSION: The high incidence of hemorrhoids obliges the development of new molecules; therefore, safe and efficient drugs to confer protection against hemorrhoids are urgently needed. This review article mainly focuses on the newer molecules to overcome hemorrhoids and also emphasizes various studies carried out in the past.

Role of Medicinal Plants in the Management of Inflammatory Disorders: An Overview.

Owing to the enhanced toxicity as well as consequences of allopathic medication, the research on herbal therapies is developing progressively. As a result, medicinal herbs are beginning to play a substantial role in the advancement of the dominant therapeutic medications. Since ancient times, the use of herbs has performed a vital part in human well-being as well in the invention of cutting-edge pharmaceuticals. Inflammation and related illnesses are a major health concern for the entire human population. Pain-inducing drugs including opiates, non-steroidal anti-inflammatory drugs, glucocorticoids, and corticosteroids have severe side effects and these therapies suffer from the recurrence of symptoms too after discontinuing the treatment. As a result, the diagnosis along with the advancement of medications with anti-inflammatory properties is the priority to conquer the drawbacks of the existing therapies. The present review article provides insight into the literature comprising promising phytochemicals from various medicinal plants tested through different model systems and employed for alleviating inflammation in several inflammatory disorders as well as clinical status of the herbal products.

Bakuchiol: A Potential Anticancer Compound from Psoralea corylifolia Linn.

BACKGROUND: Bakuchiol is a monoterpene phenol isolated from the seeds of Psoralea corylifolia Linn. It is used traditionally in Indian and Chinese medicine and has been reported to possess extensive pharmacological potential against a variety of ailments. A recent study enumerates the anticancer potential of bakuchiol. OBJECTIVE: The objective of the present review study is to explore the anticancer potential of bakuchiol which provides insight into the design and develop novel molecular entities against various disorders. METHODS: Current prose and patents emphasizing the anticancer potential of bakuchiol have been identified and reviewed with particular emphasis on their scientific impact and novelty. An extensive literature survey was performed and compiled via the search engine, PubMed, Science Direct, and from many reputed foundations. RESULTS: The study's findings suggested and verified the anticancer potential that Psoralea and bakuchiol against a variety of cancer. Both Psoralea and bakuchiol also portrayed synergistic or potentiating effects when given in combination with other anticancer drugs or natural compounds. CONCLUSION: Altogether, the promising anticancer potential of bakuchiol may open new probes for therapeutic invention in various types of tumors. Thus, the present review gives the erudition of bakuchiol and Psoralea as anticancer which paves the way for further work in exploring their potential.

Targeting human Glucokinase for the treatment of type 2 diabetes: an overview of allosteric Glucokinase activators.

Diabetes mellitus is a worldwide impacting disorder and the ratio through which the number of diabetic patients had increased worldwide, puts medical professionals to serious stress for its effective management. Due to its polygenic origin and involvement of multiple genes to its pathophysiology, leads to understanding of this ailment more complex. It seems that current interventions, such as dietary changes, life style changes and drug therapy such as oral hypoglycaemics and insulin, are unable to halt the trend. There are various novel and emerging targets on which the researchers are paying attention to combat with this ailment successfully. Human glucokinase (GK) enzyme is one of these novel and emerging targets for management of diabetes. Its availability in the pancreas and liver cells makes this target more lucrative. GK's presence in the pancreatic and hepatic cells plays a very important function for the management of glucose homoeostasis. Small molecules that activate GK allosterically provide an alternative strategy for restoring/improving glycaemic regulation, especially in type 2 diabetic patients. Although after enduring many setbacks in the development of the GK activators, interest has been renewed especially due to introduction of novel dual acting GK activator dorzagliatin, and a novel hepato-selective GK activator, TTP399. This review article has been formulated to discuss importance of GK in glucose homeostasis, recent updates on small molecules of GK activators, clinical status of GK activators and challenges in development of GK activators.

COVID-19 and diabetes: Association intensify risk factors for morbidity and mortality.

Diabetes is a condition that affects a large percentage of the population and it is the leading cause of a wide range of costly complications. Diabetes is linked to a multi-fold increase in mortality and when compared to non-diabetics, the intensity and prevalence of COVID-19 ailment among diabetic individuals are more. Since its discovery in Wuhan, COVID-19 has grown rapidly and shown a wide range of severity. Temperature, lymphopenia, non-productive cough, dyspnoea, and tiredness are recognized as the characteristic of individuals infected with COVID-19 disease. In COVID-19 patients, diabetes and other related comorbidities are substantial predictors of disease and mortality. According to a recent study, SARS-CoV-2 (the virus responsible for covid-19 disease) may also lead to direct pancreatic harm, which could aggravate hyperglycemia and potentially cause the establishment of diabetes in formerly non-diabetic individuals. This bidirectional association of COVID-19 and diabetes load the burden on health care professionals throughout the world. It is recommended that gliptin medications be taken moderately, blood glucose levels must be kept under control, ACE inhibitors should be used in moderation, decrease the number of avoidable hospitalizations, nutritional considerations, and some other prevention measures, such as immunization, are highly recommended. SARS-CoV-2 may cause pleiotropic changes in glucose homeostasis, which could exacerbate the pathophysiology of pre-existing diabetes or result in new disease processes.

Natural alkaloids targeting EGFR in non-small cell lung cancer: Molecular docking and ADMET predictions.

The phytochemicals contribute to the processes of protection and interaction by acting as antioxidants, anti-mutagens, anticarcinogens, and antimicrobial agents. Among the diverse families of phytoconstituents, alkaloids play an essential role in medicine. These are low-molecular-mass compounds containing nitrogen and are generally alkaline. In this study, in silico molecular docking was performed using AutoDock Vina for thirty-one alkaloids against epidermal growth factor receptor (EGFR). Erlotinib was used as a reference ligand for this study. Erlotinib has been linked to various serious side effects over the past decade, including folliculitis, diarrhoea, paronychia, fatigue, conjunctivitis, ectopion, and epiphora of the lower eyelids. This study found sanguinarine (-10.7 kcal mol-1) to be the most potent inhibitor of EGFR as compared to erlotinib (-7.5 kcal mol-1). Other alkaloids namely, isocolumbin (-9.3 kcal mol-1), lunamarine (-9.1 kcal mol-1), ajmaline (-8.6 kcal mol-1), magnoflorine (-8.6 kcal mol-1) and jatrorrhizine (-8.5 kcal mol-1) also showed potent inhibition against EGFR, but the stability of these molecules with EGFR was less than sanguinarine and more than erlotinib. These were stable and ideal pharmaceutical alkaloids because of their significant interactions, minimal Gibbs free energy, safety, effectiveness and selectivity. Amongst the 31 alkaloids subjected to ADMET prediction, 29 alkaloids followed Lipinski's rule of five. These 29 alkaloids were predicted to have high bioavailability, high lead-likeness score, low toxicity and were easier to synthesize. Compared to erlotinib, other molecules showed less or no inhibition of EGFR. The six named compounds listed above may be potent inhibitors for EGFR mutated cancers, as for example non-small cell lung cancer, colorectal cancer, and pancreatic cancer.

An extensive review on phytochemistry and pharmacological activities of Indian medicinal plant Celastrus paniculatus Willd.

Celastrus paniculatus is a traditional herb belonging to the family Celastraceae and is widely used for a number of medicinal activities in the Indian Unani and Ayurvedic systems. In this study, the extensive literature search was carried out on phytochemistry, ethnobotanical uses and pharmacological activities of C. paniculatus (Willd.) in various scientific databases as well as patents. Research on phytochemical investigation has shown the presence of monoterpenes (linalool, α-terpinyl acetate, nerol acetate), sesqueterpene esters (such as malkanguniol, malkangunin, valerenal, globulol, viridiflorol, cubenol and agarofuran derivatives), diterpenoids (such as phytone, isophytol), triterpenoids (such as lupeol, pristimerin, paniculatadiol, zeylasteral, zeylasterone, ß-amyrin, squalene), alkaloids (celapanin, celapanigin, celapagin, paniculatine, celastrine, maymyrsine), fatty acids, steroids (ß-sitosterol, carpesterol benzoate), flavonoids (paniculatin), benzoic acid, and vitamin C in this plant. All the reported pharmacological activities of this plant could be due to the presence of these phytochemicals. This plant possesses strong antioxidant activity which includes total flavonoid content, total phenolic content, nitric oxide scavenging activity and free radical scavenging activity. This plant possesses multiple pharmacological activities including cognition-enhancing, neuroprotective, antipsychotic, anti-depressant, antibacterial, anti-arthritic, anti-malarial, analgesic, anti-inflammatory, anti-fertility, cardiovascular, locomotor, anxiolytic, wound healing activity, anti-spasmodic, hypolipidemic, anti-cancerous and iron-chelating activity with different extracts of this plant as well as various phytoconstituents present in this plant. The objective of this review article is to discuss in detail the reported ethnopharmacological uses, phytochemistry and various pharmacological activities of C. paniculatus.

Role of phytoconstituents in the management of COVID-19.

BACKGROUND: COVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas. SCOPE AND APPROACH: This review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry through host cell receptors. The use of medicinal plants containing specific phytomoieties could be seen in providing a safer and long-term solution for the population with lesser side effects. Key Findings and Conclusions: Considering the high cost and time-consuming drug discovery process, therapeutic repositioning of existing drugs was explored as treatment option in COVID-19, however several molecules have been retracted as therapeutics either due to no positive outcomes or the severe side effects. These effects call for exploring the alternate treatment options which are therapeutically effective as well as safe. Keeping this in mind, phytopharmaceuticals derived from medicinal plants could be explored as important resources in the development of COVID-19 treatment, as their role in the past for treatment of viral diseases like HIV, MERS-CoV, and influenza has been well reported. Considering this fact, different phytoconstituents such as flavonoids, alkaloids, tannins and glycosides etc. Possessing antiviral properties against coronaviruses and possessing potential against SARS-CoV-2 have been reviewed in the present work.

Alcoholic and Non-Alcoholic Liver Diseases: Promising Molecular Drug Targets and their Clinical Development.

Alcoholic and non-alcoholic fatty liver diseases have become a serious concern worldwide. Both these liver diseases have an identical pathology, starting from simple steatosis to cirrhosis and, ultimately to hepatocellular carcinoma. Treatment options for alcoholic liver disease (ALD) are still the same as they were 50 years ago which include corticosteroids, pentoxifylline, antioxidants, nutritional support and abstinence; and for non-alcoholic fatty liver disease (NAFLD), weight loss, insulin sensitizers, lipid-lowering agents and anti-oxidants are the only treatment options. Despite broad research in understanding the disease pathophysiology, limited treatments are available for clinical use. Some therapeutic strategies based on targeting a specific molecule have been developed to lessen the consequences of disease and are under clinical investigation. Therefore, focus on multiple molecular targets will help develop an efficient therapeutic strategy. This review comprises a brief overview of the pathogenesis of ALD and NAFLD; recent molecular drug targets explored for ALD and NAFLD that may prove to be effective for multiple therapeutic regimens and also the clinical status of these promising drug targets for liver diseases.