Aldose Reductase Research Articles

Vitamin C alleviates hyperglycemic stress in retinal pigment epithelial cells.

Retinal pigment epithelial cells (RPECs) are a type of retinal cells that structurally and physiologically support photoreceptors. However, hyperglycemia has been shown to play a critical role in the progression of diabetic retinopathy (DR), which is one of the leading causes of vision impairment. In the diabetic eye, the high glucose environment damages RPECs via the induction of oxidative stress, leading to the release of excess reactive oxygen species (ROS) and triggering apoptosis. In this study, we aim to investigate the antioxidant mechanism of Vitamin C in reducing hyperglycemia-induced stress and whether this mechanism can preserve the function of RPECs. ARPE-19 cells were treated with high glucose in the presence or absence of Vitamin C. Cell viability was measured by MTT assay. Cleaved poly ADP-ribose polymerase (PARP) was used to identify apoptosis in the cells. ROS were detected by the DCFH-DA reaction. The accumulation of sorbitol in the aldose reductase (AR) polyol pathway was determined using the sorbitol detection assay. Primary mouse RPECs were isolated from adult mice and identified by Rpe65 expression. The mitochondrial damage was measured by mitochondrial membrane depolarization. Our results showed that high glucose conditions reduce cell viability in RPECs while Vitamin C can restore cell viability, compared to the vehicle treatment. We also demonstrated that Vitamin C reduces hyperglycemia-induced ROS production and prevents cell apoptosis in RPECs in an AR-independent pathway. These results suggest that Vitamin C is not only a nutritional necessity but also an adjuvant that can be combined with AR inhibitors for alleviating hyperglycemic stress in RPECs.

Drug synthesis, separation, and identification of a di-stereoisomeric mixture of spiro-oxalidinonic derivatives of sorbinil by high-performance liquid chromatography

A straightforward and sensitive method for high-performance liquid chromatography (HPLC) was created in order to separate and identify the di-stereoisomeric mixture of a spiro-oxalidinonic derivative of sorbinil. HPLC was carried out using a C18 reversed-phase column. The mobile phase used in the isocratic elution process was a 70:30 v/v combi¬nation of methanol and acetonitrile flowed at a rate of 2 mL/min. The procedure delivered the best result among the various attempts made. Two peaks were identified on the chromatogram, attributable to the two di-stereoisomers of the mixture analysed. Analogues of sorbinil, a powerful inhibitor of aldose reductase, have been synthesized and further tested on aldose reductase as mixtures of di-stereoisomers, exhibiting an IC50 in the order of the micromolar. The structure of the compounds was checked with nuclear magnetic resonance spectroscopy. The chemical shifts were expressed in ppm scale δ.

QUBO Problem Formulation of Fragment-Based Protein–Ligand Flexible Docking

Protein–ligand docking plays a significant role in structure-based drug discovery. This methodology aims to estimate the binding mode and binding free energy between the drug-targeted protein and candidate chemical compounds, utilizing protein tertiary structure information. Reformulation of this docking as a quadratic unconstrained binary optimization (QUBO) problem to obtain solutions via quantum annealing has been attempted. However, previous studies did not consider the internal degrees of freedom of the compound that is mandatory and essential. In this study, we formulated fragment-based protein–ligand flexible docking, considering the internal degrees of freedom of the compound by focusing on fragments (rigid chemical substructures of compounds) as a QUBO problem. We introduced four factors essential for fragment–based docking in the Hamiltonian: (1) interaction energy between the target protein and each fragment, (2) clashes between fragments, (3) covalent bonds between fragments, and (4) the constraint that each fragment of the compound is selected for a single placement. We also implemented a proof-of-concept system and conducted redocking for the protein–compound complex structure of Aldose reductase (a drug target protein) using SQBM+, which is a simulated quantum annealer. The predicted binding pose reconstructed from the best solution was near-native (RMSD=1.26 Å), which can be further improved (RMSD=0.27 Å) using conventional energy minimization. The results indicate the validity of our QUBO problem formulation.

Cellular and Molecular Mechanisms of Neuronal Degeneration in Early-Stage Diabetic Retinopathy.

Studies on the early retinal changes in Diabetic Retinopathy (DR) have demonstrated that neurodegeneration precedes vascular abnormalities like microaneurysms or intraretinal hemorrhages. Therefore, there is a growing field of study to analyze the cellular and molecular pathways involved to allow for the development of novel therapeutics to prevent the onset or delay the progression of DR. Molecular Mechanisms: Oxidative stress and mitochondrial dysfunction contribute to neurodegeneration through pathways involving polyol, hexosamine, advanced glycation end products, and protein kinase C. Potential interventions targeting these pathways include aldose reductase inhibitors and protein kinase C inhibitors. Neurotrophic factor imbalances, notably brain-derived neurotrophic factor and nerve growth factor, also play a role in early neurodegeneration, and supplementation of these neurotrophic factors show promise in mitigating neurodegeneration. Cellular Mechanisms: Major cellular mechanisms of neurodegeneration include caspase-mediated apoptosis, glial cell reactivity, and glutamate excitotoxicity. Therefore, inhibitors of these pathways are potential therapeutic avenues. Vascular Component: The nitric oxide pathway, critical for neurovascular coupling, is disrupted in DR due to increased reactive oxygen species. Vascular Endothelial Growth Factor (VEGF), a long-known angiogenic factor, has demonstrated both damaging and neuroprotective effects, prompting a careful consideration of long-term anti-VEGF therapy. Current DR treatments primarily address vascular symptoms but fall short of preventing or halting the disease. Insights into the mechanisms of retinal neurodegeneration in the setting of diabetes mellitus not only enhance our understanding of DR but also pave the way for future therapeutic interventions aimed at preventing disease progression and preserving vision.

Exploring the Molecular Docking Interactions between the Polyherbal Formulation Ibadhychooranam and Human Aldose Reductase Enzyme as a Novel Approach for Investigating its Potential Efficacy in Management of Cataract

Background: Kannir sirandha urupillai... which means no organ is better than eye. Eye health and treatment have held significant importance in the Siddha system of medicine since ancient times, emphasizing the holistic approach to well-being encompassing physical, mental, and spiritual aspects. Eye disease is classified into 96 types and their ethology, treatment method, preventive measures all are explained in many of the Siddha literature. Among them cataract is one of the leading cause of blindness which is characterised by clouding of eye’s natural lens, leading to blurry, foggy or flimy vision. This paper will elaborates about the docking analysis of poly herbal formulation Ibadhy chooranam against Human aldose reductase enzyme for cataract.  Aim & Objective: The aim of this study is to investigate the potential efficacy of the polyherbal formulation IbadhyChooranam in preventing or treating cataracts through molecular docking analysis of its interactions with the human aldose reductase enzyme.  Methodology: Docking simulations were conducted for the extracted phytoconstituents of IbadhyChooranam against the Human Aldose Reductase Enzyme. AutoDock tools were utilized to incorporate hydrogen atoms, Coleman united atom type charges, and solvation parameters. The docking process employed the Lamarckian genetic algorithm along with the Solis & Wets Local Search method to simulate ligand-receptor interactions.  Result: The current study revealed that phytochemicals present in IbadhyChooranam, including Nerolidol, Ellagic acid, Phyllanthin, Costunolide, Embelin, Cyperolone, Zingiberene, Piperic acid, Piperine, and Lupeol, exhibited between 6 to 9 significant interactions with residual amino acids in the aldose reductase enzyme. In comparison, the standard drug Epalrestat demonstrated 8 viable interactions with the residual amino acids of the aldose reductase enzyme.  Conclusion: According to the computational analysis findings, it can be inferred that the bioactive compounds present in IbadhyChooranam exhibit notable binding affinity towards the target aldose reductase enzyme. Ibadhy chooranam inhibit the function of aldose reductase enzyme which delay the sorbitol accumulation and subsequent cataract development. Through this study, it was also justified that the Ibadhy chooranam possess significant anti-cataract activity.

Synthesis and anti-inflammatory activity of benzimidazole derivatives; an in vitro, in vivo and in silico approach

Many non-steroidal anti-inflammatory drugs (NSAIDs) concurrently inhibit both COX-1 and COX-2, with a preference for specifically targeting COX-2 due to its significant involvement in various pathologies. In addition to COX enzymes, several other targets, including Aldose reductase, Aldo-ketoreductase family 1-member C2, and Phospholipase A2, have been identified as contributors to inflammation and a myriad of other diseases.In this context, a series of 2-substituted benzimidazole derivatives was synthesized and assessed for their anti-inflammatory potential through both in vitro and in vivo assays. Molecular docking studies were conducted to elucidate the mechanism of action of these compounds against COX enzymes and other therapeutic targets associated with NSAIDs, such as Aldose reductase, AIKRC, and Phospholipase A2.Among the synthesized compounds, B2, B4, B7, and B8 demonstrated IC50 values lower than the standard ibuprofen, as determined by the Luminol-enhanced chemiluminescence assay. Validation of these findings was achieved through an in vivo carrageenan-induced mice paw edema model, confirming a comparable anti-inflammatory effect to diclofenac sodium observed in vitro. Notably, these compounds exhibited significant binding affinity with all therapeutic targets investigated in this study.These results suggest that the newly synthesized derivatives possess noteworthy anti-inflammatory potential, warranting further exploration for the development of novel multi-targeting inhibitors.

Discovery of Novel Aldose Reductase Inhibitors via the Integration of Ligand-Based and Structure-Based Virtual Screening with Experimental Validation.

Aldose reductase plays a central role in diabetes mellitus (DM) associated complications by converting glucose to sorbitol, resulting in a harmful increase of reactive oxygen species (ROS) in various tissues, such as the heart, vasculature, neurons, eyes, and kidneys. We employed a comprehensive approach, integrating both ligand- and structure-based virtual screening followed by experimental validation. Initially, candidate compounds were extracted from extensive drug and chemical libraries using the DeepChem's GraphConvMol algorithm, leveraging its capacity for robust molecular feature representation. Subsequent refinement employed molecular docking and molecular dynamics (MD) simulations, which are crucial for understanding compound-receptor interactions and dynamic behavior in a simulated physiological environment. Finally, the candidate compounds were subjected to experimental validation of their biological activity using an aldose reductase inhibitor screening kit. The comprehensive approach led to the identification of a promising compound, demonstrating significant potential as an aldose reductase inhibitor. This comprehensive approach not only yields a potential therapeutic intervention for DM-related complications but also establishes an integrated protocol for drug development, setting a new benchmark in the field.

Benchmarking docking, density functional theory and molecular dynamics studies to assess the aldose reductase inhibitory potential of Trigonella foenum-graecum compounds for managing diabetes-associated complications

Inhibition of aldose reductase (AR) could be a beneficial strategy for managing diabetes-associated complications. Trigonella foenum-graecum (TFG) is used around the globe as a traditional medicine for the management of diabetes. Our study aimed to assess the potential of TFG phytocompounds as inhibitors of AR in the context of diabetes-related complications. Our research work employed molecular docking, density functional theory (DFT) and molecular dynamics (MD) to evaluate the efficacy of TFG compounds. The study compared the predictive power of AutoDock and AutoDock Vina docking software and found that AutoDock Vina performs better in ranking and discriminating actives and decoys. The research identified five compounds as potential AR inhibitors from fifty-eight reported TFG phytoconstituents. Tigogenin and Gitogenin stood out as the most promising AR inhibitors. The electronic properties of the compounds were analysed through DFT studies and provided insights into their binding potential. Finally, the results of MD simulations indicated that Tigogenin and Gitogenin bound robustly with AR throughout the simulation period. This study predicted the AR inhibitory potential of TFG compounds for managing diabetes-associated complications and supports further drug development from TFG. The benchmarking approach used in this study improves the accuracy and dependability of bioactivity prediction.

Bioactivity of 2-(3,4-Dihydroxyphenyl)-5,7-dihydroxy-2,3-dihydrochromen-4-one from pistacia chinensis on ENPP1 and aldose reductase

Pistacia chinensis is used as a decorative tree and currently studied as a source of biofuels. Besides, its parts and extracts are endowed with several therapeutic uses which have been widely explored in traditional medicine and that are related to its rich composition in phytochemicals. Molecular docking and enzymatic inhibition tests were used to study the activity of eriodictyol, a flavonoid extracted from the barks of P. chinensis, against ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and aldose reductase (ALR2). The compound was highlighted as a micromolar inhibitor in vitro (IC50 = 263.76 ± 1.32 µM and 4.21 ± 0.94 µM, respectively) and docking showed that eriodictyol efficiently targets the binding sites of the enzymes. In conclusion, this study unveils the potential of eriodictyol on enzymes that are involved in immunostimulation and in complications of diabetes mellitus.

Luminescent Supramolecular Metallogels: Drug Loading and Eu(III) as Structural Probe.

Supramolecular metallogels combine the rheological properties of gels with the color, magnetism, and other properties of metal ions. Lanthanide ions such as Eu(III) can be valuable components of metallogels due to their fascinating luminescence. In this work, we combine Eu(III) and iminodiacetic acid (IDA) into luminescent hydrogels. We investigate the tailoring of the rheological properties of these gels by changes in their metal:ligand ratio. Further, we use the highly sensitive Eu(III) luminescence to obtain information about the chemical structure of the materials. In special, we take advantage of computational calculations to employ an indirect method for structural elucidation, in which the simulated luminescent properties of candidate structures are matched to the experimental data. With this strategy, we can propose molecular structures for different EuIDA gels. We also explore the usage of these gels for the loading of bioactive molecules such as OXA, observing that its aldose reductase activity remains present in the gel. We envision that the findings from this work could inspire the development of luminescent hydrogels with tunable rheology for applications such as 3D printing and imaging-guided drug delivery platforms. Finally, Eu(III) emission-based structural elucidation could be a powerful tool in the characterization of advanced materials.

Ethnomedicinal importance of Patuletin in Medicine: Pharmacological Activities and Analytical Aspects.

Plant-derived bioactive molecules have been a major source of therapeutics for human and veterinarian purposes. Different traditional medicine system across the globe had relied on natural resources to meet their demand of healthcare. Still in modern world pharmaceutical industries look for phytochemicals to develop new drugs. The current review explores patuletin, a flavonoid for its diverse reported pharmacological activities along with its analytical techniques. Scientific data published on patuletin was collected from Scopus, Science Direct, Pubmed, Google, and Google Scholar. The collected data were analyzed and arranged as per specific pharmacological activities performed using in-vitro or in-vivo methods. Analytical methods of patuletin have been presented next to pharmacological activities, Results: Available scientific literature indicates patuletin has anti-inflammatory, cytotoxic, genotoxic, hepatoprotective, antiproliferative, antiplatelet, antinociceptive, and antioxidant activity. In addition to these activities, its biological potential on breast cancer, rheumatoid arthritis, aldose reductase, and different types of microorganisms has been also presented in this work. Analytical data on patuletin signified the importance of patuletin for the standardization of herbal products and derived medicine. It may be concluded that patuletin with its diverse biological activities and readily available analytical methods, holds the potential to be translated into a new drug entity.

Antioxidant Properties and Aldose Reductase Inhibitory Potency of Viscum album L. Extracts: Experimental and Computational Insights

Antioxidant Properties and Aldose Reductase Inhibitory Potency of Viscum album L. Extracts: Experimental and Computational Insights

Quantification of total phenols in Coleus forskohlii and Inhibition of Aldose Reductase by Rosmarinic acid.

Many complications of diabetes have been associated with the accumulation of intracellular sorbitol caused by excessive activity of aldose reductase (ALR2). ALR2 is a member of the aldo-keto reductases (AKR) superfamily and has gained significant attention due to its role in the development of diabetic complications. Inhibiting ALR2 could help prevent or delay some of these problems. Coleus forskohlii is a natural medicinal plant that is known for its medicinal effects and is also used as a beverage in several European countries. High-performance liquid chromatography (HPLC) was used to measure the polyphenol content of aqueous leaf extracts of C. forskohlii, and it was found that rosmarinic acid (RA) had the highest concentration (1.25 mg/g) compared to other polyphenols. In vitro bioassays were conducted to evaluate the inhibitory effect of RA on ALR2. RA significantly and dose-dependently reduced the build-up of sorbitol in human erythrocytes under high glucose conditions. Molecular docking studies suggest that RA, which is an essential polyphenol, could be a potential ALR2 inhibitor. This study is the first to show that RA has an IC50 value of 56% to exhibit an inhibitory effect against ALR2.

Randomized Trial of a Selective Aldose Reductase Inhibitor in Patients With Diabetic Cardiomyopathy

Randomized Trial of a Selective Aldose Reductase Inhibitor in Patients With Diabetic Cardiomyopathy

Aldose Reductase as a Key Target in the Prevention and Treatment of Diabetic Retinopathy: A Comprehensive Review.

The escalating global prevalence of diabetes mellitus (DM) over the past two decades has led to a persistent high incidence of diabetic retinopathy (DR), necessitating screening for early symptoms and proper treatment. Effective management of DR aims to decrease vision impairment by controlling modifiable risk factors including hypertension, obesity, and dyslipidemia. Moreover, systemic medications and plant-based therapy show promise in advancing DR treatment. One of the key mechanisms related to DR pathogenesis is the polyol pathway, through which aldose reductase (AR) catalyzes the conversion of glucose to sorbitol within various tissues, including the retina, lens, ciliary body and iris. Elevated glucose levels activate AR, leading to osmotic stress, advanced glycation end-product formation, and oxidative damage. This further implies chronic inflammation, vascular permeability, and angiogenesis. Our comprehensive narrative review describes the therapeutic potential of aldose reductase inhibitors in treating DR, where both synthetic and natural inhibitors have been studied in recent decades. Our synthesis aims to guide future research and clinical interventions in DR management.

Prunin from Poncirus trifoliata (L.) Rafin Inhibits Aldose Reductase and Glucose-Fructose-Mediated Protein Glycation and Oxidation of Human Serum Albumin.

Diabetes complications are associated with aldose reductase (AR) and advanced glycation end products (AGEs). Using bioassay-guided isolation by column chromatography, 10 flavonoids and one coumarin were isolated from Poncirus trifoliata Rafin and tested in vitro for an inhibitory effect against human recombinant AR (HRAR) and rat lens AR (RLAR). Prunin, narirutin, and naringin inhibited RLAR (IC50 0.48-2.84 μM) and HRAR (IC50 0.68-4.88 μM). Docking simulations predicted negative binding energies and interactions with the RLAR and HRAR binding pocket residues. Prunin (0.1 and 12.5 μM) prevented the formation of fluorescent AGEs and nonfluorescent Nε-(carboxymethyl) lysine (CML), as well as the fructose-glucose-mediated protein glycation and oxidation of human serum albumin (HSA). Prunin suppressed the formation of the β-cross-amyloid structure of HSA. These results indicate that prunin inhibits oxidation-dependent protein damage, AGE formation, and AR, which may help prevent diabetes complications.

Cumin (Cuminum cyminum L.) an export-oriented Indian seed spice with inherent nutraceutical and therapeutic attributes: A review

Cumin seeds and value-added products are used in beverages, liquors,candy, nutraceuticals, therapeutics, toiletries, perfumery and lotions. In theIndian systems of medicine, cumin finds a vital role through its essential &total oil components and various aqueous and alcoholic extracts. Cuminseeds contain volatile oil (3–4%), the primary active principles of which arecumin aldehyde, terpenes (45–50%), phenols, unsaturated and saturatedfatty acids, etc., those occur in varying fractions compensating each other,which act as a scavenger for free radicals and antioxidants. As anutraceutical, cumin seeds contain plenty of iron, magnesium, calcium,manganese, and phosphorus. The vitamins present include thiamine,riboflavin, niacin, vitamin A, C, E, K, and vitamin B6. The seedspossessdiuretic, carminative, stimulant, digestive, tonic, appetizer, stomachic andastringent properties. It is traditionally an essential critical remedial agentfor digestion, diarrhoea, leucorrhoea, eczema, atonic, flatulence,dyspepsia and abdominal pains. Phytochemicals like alkaloid, coumarin,anthraquinone, flavonoid, protein, glycoside, resin, saponin, tannin andsteroids are abundant in its seed. Cumin seed extracts bear variousmedicinal properties such as insecticidal, antimicrobial, anti-inflammatory,antioxidant, antidiabetic, anticancer, hypotensive, bronchodilator,immunological, contraceptive, aldose reductase, analgesic,alpha-glucosidase and tyrosinase inhibitory effects, etc. Thus use of cumin offerscombined advantages, providing both nutraceutical and therapeuticproperties simultaneously.

Xanthones with multiple roles against diabetes: their synthesis, structure-activity relationship, and mechanism studies.

A four-step synthetic process has been developed to prepare 1,3,5,8-tetrahydroxyxanthone (2a) and its isomer 1,3,7,8-tetrahydroxyxanthone (2b). 25 more xanthones were also synthesized by a modified scheme. Xanthone 2a was identified as the most active inhibitor against both α-glucosidase and aldose reductase (ALR2), with IC50 values of 7.8 ± 0.5 μM and 63.2 ± 0.6 nM, respectively, which was far active than acarbose (35.0 ± 0.1 μM), and a little more active than epalrestat (67.0 ± 3.0 nM). 2a was also confirmed as the most active antioxidant in vitro with EC50 value of 8.9 ± 0.1 μM. Any structural modification including methylation, deletion, and position change of hydroxyl group in 2a will cause an activity loss in inhibitory and antioxidation. By applying a H2 O2 -induced oxidative stress nematode model, it was confirmed that xanthone 2a can be absorbed by Caenorhabditis elegans and is bioavailable to attenuate in vivo oxidative stress, including the effects on lifespan, superoxide dismutase, Catalase, and malondialdehyde. 2a was verified with in vivo hypoglycemic effect and mitigation of embryo malformations in high glucose. All our data support that xanthone 2a behaves triple roles and is a potential agent to treat diabetic mellitus, gestational diabetes mellitus, and diabetic complications.

Exploring the therapeutic mechanism of potential phytocompounds from Kalanchoe pinnata in the treatment of diabetes mellitus by integrating network pharmacology, molecular docking and simulation approach

Since ancient times, bioactive phytocompounds from different parts of medicinal plants have been used to heal various disease ailments and they are now regarded as a valuable source of disease prevention globally.Kalanchoe pinnatais a member of the Crassulaceae family; it has a long history of usage in traditional ayurvedic treatment. Analysis of bioactive compounds for their potential anti-type-2 diabetes mellitus (T2DM) mechanism along within-vitroandin-silicoapproaches was studied in the present research. The alpha-amylase and alpha-glucosidase inhibitory activity of methanolic extract of Kalanchoe pinnata (α-amylase: IC50 29.50 ± 0.04 μg/ml; α-glucosidase IC50 32.04 ± 0.35 μg/ml) exhibit a high degree of similarity to the standard drug acarbose (IC50 35.82 ± 0.14 μg/ml). Different biological databases were used to list phytocompounds from the plant, and ADME analysis using swissADME was carried out to screen compounds that obeyed the Lipinski rule of 5 and were employed further. STRING and KEGG pathway analysis was performed for gene enrichment analysis followed by network pharmacology to identify key target proteins involved in DM. AMY2A, NOX4, RPS6KA3, ADRA2A, CHRM5, and IL2 were identified as core targets for luteolin, kaempferol, alpha amyrin, stigmasterol compounds by modulating neuroactive ligand interaction, P13-AKT, MAPK, and PPAR signaling pathways. Molecular docking was performed to study the binding affinity among bioactive compounds ofK. pinnataagainst aldose reductase, alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase IV. Alpha-amylase-friedelin [FRI] and alpha-amylase-acarbose [STD] complexes were subjected to molecular simulation for a 200 ns duration that depicted the stability of the compounds and proteins. In the current study, employing dual approach in-silico and in-vitroenzyme assays has yielded a comprehensive and strong understanding of its potential therapeutic properties, making a significant step towards the development of novel anti-diabetic treatment.

Pharmacological evaluation and phytochemical profiling of butanol extract of L. edodes with in- silico virtual screening

L. edodes (L. edodes) is the most consumed mushroom in the world and has been well known for its therapeutic potential as an edible and medicinal candidate, it contains dietary fibers, vitamins, proteins, minerals, and carbohydrates. In the current study butanolic extract of mushroom was used to form semisolid butanol extract. The current study aimed to explore biometabolites that might have biological activities in n-butanol extract of L. edodes using FT-IR and GC–MS and LC–MS. The synergistic properties of bioactive compounds were futher assessed by performing different biological assays such as antioxidant, anti-inflammatory and antidiabetic. FTIR spectra showed different functional groups including amide N–H group, Alkane (C-H stretching), and (C = C stretching) groups at different spectrum peaks in the range of 500 cm−1 to 5000 cm−1 respectively. GC–MS profiling of n-butanol extract depicted 34 potent biomolecules among those dimethyl; Morphine, 2TMS derivative; Benzoic acid, methyl ester 1-(2-methoxy-1-methylethoxy)-2-propanol were spotted at highest range. Results indicate that L. edodes n-butanol extract showed a maximum anti-inflammatory potential 91.4% at 300 mg/mL. Antioxidant activity was observed by measuring free radical scavenging activity which is 64.6% at optimized concentration along with good antidiabetic activity. In-silico study executed the biopotential of active ingredient morphine which proved the best docking score (− 7.0 kJ/mol) against aldose reductase. The in-silico drug design analysis was performed on biometabolites detected through GC–MS that might be a potential target for sulfatase-2 to treat ruminated arthritis. Morphine binds more strongly (− 7.9 kJ/mol) than other bioactive constituents indicated. QSAR and ADMET analysis shown that morphine is a good candidates against ruminated arthritis. The current study showed that L. edodes might be used as potent drug molecules to cure multiple ailments. As mushrooms have high bioactivity, they can be used against different diseases and to develop antibacterial drugs based on the current situation in the world in which drug resistance is going to increase due to misuse of antibiotics so new and noval biological active compounds are needed to overcome the situation.