Amphiphilic, lauric acid-coupled pluronic-based nano-micellar system for efficient glipizide delivery.

Glipizide; an insulin secretagogue belonging to the sulfonylurea class, is a widely used antidiabetic drug for managing type 2 diabetes. However, the need for life-long administration and repeated doses poses challenges in maintaining optimal blood glucose levels. In this regard, orally active sustained-release nano-formulations can be a better alternative to traditional antidiabetic formulations. The present study explored an innovative approach by formulating orally active sustained-release nano-micelles using the amphiphilic lauric acid-conjugated-F127 (LAF127) block copolymer. LAF127 block copolymer was synthesized through esterification and thoroughly characterized before being employed to develop glipizide-loaded nano-micelles (GNM) via the thin-film hydration technique. The optimized formulation exhibited mean particle size of 341.40 ± 3.21 nm and depicted homogeneous particle size distribution with a polydispersity index (PDI) < 0.2. The formulation revealed a surface charge of -17.11 ± 6.23 mV. The in vitro release studies of glipizide from developed formulation depicted a sustained release profile. Drug loaded micelles exhibited a substantial reduction in blood glucose levels in diabetic rats for a duration of up to 24 h. Notably, neither the blank nano-micelles of LAF127 nor the drug loaded micelles manifested any indications of toxicity in healthy rats. This study provides an insight on suitability of synthesized LAF127 block copolymer for development of effective oral drug delivery systems for anti-diabetic activity without any significant adverse effects.

Retraction of 'Ameliorating the Role of Aripiprazole in Memory Deficits Induced by Intracerebroventricular Streptozotocin-Induced Dementia of Alzheimer's Type'.

[This retracts the article DOI: 10.1021/acsomega.3c02550.].

Astrocyte Activation and Drug Target in Pathophysiology of Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease, which is also referred to as an autoimmune disorder with chronic inflammatory demyelination affecting the core system that is the central nervous system (CNS). Demyelination is a pathological manifestation of MS. It is the destruction of myelin sheath, which is wrapped around the axons, and it results in the loss of synaptic connections and conduction along the axon is also compromised. Various attempts are made to understand MS and demyelination using various experimental models out of them. The most popular model is experimental autoimmune encephalomyelitis (EAE), in which autoimmunity against CNS components is induced in experimental animals by immunization with self-antigens derived from basic myelin protein. Astrocytes serve as a dual-edged sword both in demyelination and remyelination. Various drug targets have also been discussed that can be further explored for the treatment of MS. An extensive literature research was done from various online scholarly and research articles available on PubMed, Google Scholar, and Elsevier. Keywords used for these articles were astrocyte, demyelination, astrogliosis, and reactive astrocytes. This includes articles being the most relevant information to the area compiled to compose a current review.

Neuroprotective potentials of Lead phytochemicals against Alzheimer's disease with focus on oxidative stress-mediated signaling pathways: Pharmacokinetic challenges, target specificity, clinical trials and future perspectives.

BACKGROUND: Alzheimer's diseases (AD) and dementia are among the highly prevalent neurological disorders characterized by deposition of beta amyloid (Aß) plaques, dense deposits of highly phosphorylated tau proteins, insufficiency of acetylcholine (ACh) and imbalance in glutamatergic system. Patients typically experience cognitive, behavioral alterations and are unable to perform their routine activities. Evidence also suggests that inflammatory processes including excessive microglia activation, high expression of inflammatory cytokines and release of free radicals. Thus, targeting inflammatory pathways beside other targets might be the key factors to control- disease symptoms and progression. PURPOSE: This review is aimed to highlight the mechanisms and pathways involved in the neuroprotective potentials of lead phytochemicals. Further to provide updates regarding challenges associated with their use and their progress into clinical trials as potential lead compounds. METHODS: Most recent scientific literature on pre-clinical and clinical data published in quality journals especially on the lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin was collected using SciFinder, PubMed, Google Scholar, Web of Science, JSTOR, EBSCO, Scopus and other related web sources. RESULTS: Literature review indicated that the drug discovery against AD is insufficient and only few drugs are clinically approved which have limited efficacy. Among the therapeutic options, natural products have got tremendous attraction owing to their molecular diversity, their safety and efficacy. Research suggest that natural products can delay the disease onset, reduce its progression and regenerate the damage via their anti-amyloid, anti-inflammatory and antioxidant potentials. These agents regulate the pathways involved in the release of neurotrophins which are implicated in neuronal survival and function. Highly potential lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin regulate neuroprotective signaling pathways implicated in neurotrophins-mediated activation of tropomyosin receptor kinase (Trk) and p75 neurotrophins receptor (p75NTR) family receptors. CONCLUSIONS: Phytochemicals especially phenolic compounds were identified as highly potential molecules which ameliorate oxidative stress induced neurodegeneration, reduce Aß load and inhibit vital enzymes. Yet their clinical efficacy and bioavailability are the major challenges which need further interventions for more effective therapeutic outcomes.

Anti-oxidant and anti-inflammatory potential of different polymer-based mesalamine delayed-release granules in TNBS-induced ulcerative colitis in wistar rats.

Ulcerative colitis (UC) is an inflammatory condition of colon characterized by severe damage to the innermost colon tissues. A number of studies described the use of medication delivery systems based on natural polymers like polysaccharides for the purpose of reaching the colon. In this research, polymer-based mesalamine delayed-release granules (DRGs) were tested for their antioxidant and anti-inflammatory efficacy against UC. Chitosan (C), pectin (P), and pectin-chitosan (PC) mesalamine (M) DRGs were prepared and characterized. Data revealed satisfactory compatibility, flow, packing properties, drug release pattern, and delayed drug release by DRGs. Wistar rats were treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS) (100 mg/kg) via rectal administration. Mesalamine and mesalamine DRGs (50 mg/kg) were administered orally separately for 14 days. Biomarkers of oxidative stress, inflammation, hematological tests, colon profile, and histopathology were performed. The findings demonstrated the good efficacy of the polysaccharides in delivering mesalamine to colon. Mesalamine and mesalamine DRGs based on various polymers showed significant antioxidant and anti-inflammatory effects in rats with UC. Mesalamine granules significantly attenuated colon lipid peroxidation, nitrites, myeloperoxidase activity, and interleukin-1ß levels, and improved anti-oxidants (GSH, SOD). Data showed upregulation of Nrf2 activity by mesalamine granules with CM-DRGs showing maximum effect. Mesalamine and different polymer-based mesalamine DRGs significantly attenuated TNBS-induced decline in body weight, ulcer severity, and colon damage. CM-DRGs showed the most pronounced ameliorative effect on colon and hematology parameters via anti-oxidant and anti-inflammatory activities. Chitosan can be used as a carrier for oral colon delivery of mesalamine in DRG formulation for enhanced therapeutic efficacy in UC.

Development and optimization of film forming non-pressurized liquid bandage for wound healing by Box-Behnken statistical design.

The goal of the current investigation was to develop a non-pressurized liquid bandage to promote the healing of wounds by using silver sulfadiazine. A three-factor three level box-behnken statistical design was employed to optimize the drug-loaded liquid bandage. Film-forming liquid bandage was developed by using ethyl-cellulose, dibutyl sebacate, and glycerol. For optimization, ethyl cellulose, dibutyl sebacate, and isopropyl myristate were taken as independent variables while tensile strength, water vapor absorption value, and drying time were taken as dependent variables. The film-forming liquid bandage was evaluated for various parameters like tensile strength, water vapor absorption value, drying time, viscosity, pH, in-vitro drug release studies, in-vivo wound healing studies, and stability studies. The optimized formulation was found with the tensile strength of 68.24 ± 0.24 MPa, water vapor absorption value of 2.00 ± 0.25 %, drying time of 1.75 ± 0.14 min, viscosity of 60 ± 0.5 cPs, pH of 6.0 ± 0.5 and good physicochemical properties with satisfactory film-forming ability. The in-vitro study shows that the release of test formulations was better than the marketed formulation. After 6 h of study, the liquid bandage and marketed formulation showed 41.02 % and 29.32 % of drug release respectively. Significant results were obtained for the in-vivo wound healing studies. Upon comparison with the control group (2.61 mm) and marketed formulation (1.44 mm), rats treated with the optimized formulation exhibited a noticeable improvement in wound contraction (0.8 mm). The liquid bandage after three months of stability testing was found to be stable with optimum. The film-forming liquid bandage was found to be an effective alternative to conventional topical preparations as it develops a thin polymeric layer on the wound and the skin around it and improves comfort for the patient by protecting the wound from external factors and physical harm.

Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats.

Traditional uses for the plant Medicago sativa (M. sativa) (Alfalfa) (Family: Fabaceae) include liver protection, antioxidant activity, and the treatment of bleeding and digestive issues. This study aims to assess the effect of ethanol extract of M. sativa (EEMS) on experimental-induced ulcers in diabetic rats. By pylorus ligation and ethanol administration, gastric ulcers were induced in diabetic rats. Five groups each consisting of six rats in each model were used. All other groups except Group I were made diabetic by giving rats alloxan (140 mg/kg i.p.). Vehicles were given to Group I (normal control) and Group II (diabetes control) rats. Group III (positive control) received ranitidine 50 mg/kg, and Group IV and V received EEMS at doses of 100 and 400 mg/kg, respectively. In the pylorus ligation and ethanol-induced stomach ulcer model of rats, the findings demonstrated that EEMS (100 mg/kg) showed a decreased ulcer index of 2.01 ± 0.41 and was found statistically significant against the diabetes control group (p < 0.001) as well as, an ulcer index of 0.68 ± 0.22 by EEMS (400 mg/kg) with a significant reduction in the ulcer index (p < 0.001). EEMS (100 and 400 mg/kg) reduce free acidity by 13.16 ± 0.65 mEq/L and 9.83 ± 0.30 mEq/L, respectively. EEMS also showed a protective impact on the liver and kidneys of diabetic rats. Antihyperglycemic action was also discovered in diabetic animals. The findings of the current investigation demonstrated that ethanolic extract of M. sativa possesses anti-ulcer activity in diabetic rats. Ethanolic extract of M. sativa may be a treatment option for stomach ulcers that also have diabetes.

Phytochemical profiling and biological activities of Diplazium esculentum (Retz.) Sw.: an edible vegetable fern.

OBJECTIVES: Diplazium esculentum (Retz.) Sw. is an edible vegetable fern of the Himalayan region with high nutritional and therapeutic value owing to its richness in various secondary metabolites and both macro and micronutrients. CONTENT: This updated review discusses the general traditional use, ethnopharmacology, phytochemistry, nutritional value, pharmacology, and toxicity concerns of D. esculentum. SUMMARY: The plant parts, viz. rhizomes, shoots, fronds and leaves, have immense ethnomedicinal importance, being traditionally used to cure several health disorders. Among other pharmacological effects, this botanical reveals excellent anti-inflammatory, analgesic, antifungal, antibacterial, antioxidant, anti-leishmanial, antioxidant, anaphylactic, antipyretic, anthelmintic and hepatoprotective activities, directly attributed to the presence of many secondary metabolites. From a pharmacological point of view, the excellent antioxidant potential of D. esculentum suggests its promising use for nutraceutical or functional food formulation purposes. OUTLOOK: Considering the evidences on popular ethnomedicinal uses of D. esculentum as an edible vegetable, its immense bio-potential, and multiple pharmacological roles, there is a huge need to evaluate its therapeutic applications in light of standard clinical trials.

Isolation, characterization, development and evaluation of phytoconstituent based formulation for diabetic neuropathy.

Background: Morus alba Linn, referred to as white mulberry, is a potential traditional medicine for diabetes and neuroprotection. Aim: Isolation, characterization, development and evaluation of phytoconstituent based formulation for diabetic neuropathy. Material and methods: The stem Bark of M. alba was peeled and subjected to extraction. A phytoconstituent was then isolated by column chromatography and characterized using Mass spectroscopy, FTIR, and NMR. The isolated phytoconstituent was used to formulate a nanoemulsion. Nanoemulsion was also characterized for viscosity, surface tension, refractive index, pH, and particle size. Selected nanoemulsion formulations were then tested for acute oral toxicity and diabetic neuropathy, including behavioral, hematological, histopathological, and biomarker examinations. Results: The spectral analysis affirmed that the isolated compound was found to be chrysin. A nanoemulsion formulation was made using the chrysin and was characterized and found to be stable during the stability testing and fulfilled all other testing parameters. Then acute oral toxicity study of the formulations was found to be safe. Formulations were found to possess significant results against diabetic neuropathy in rats. Biomarkers were analyzed for their mechanistic involvement in reducing neuropathy in rats, and it was found that the oxidative pathway was considerably restored, suggesting that chrysin causes these effects via this pathway. Conclusions: Results suggests that isolated phytoconstituent (chrysin) from the bark of Morus alba derived nanoemulsion has protective and beneficial effects by diminishing the oxidative damage against alloxan-induced diabetic neuropathy in rats.

Ameliorating the Role of Aripiprazole in Memory Deficits Induced by Intracerebroventricular Streptozotocin-Induced Dementia of Alzheimer's Type.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder causing immense suffering for the patients. Dopamine D2 and 5-hydroxytryptamine receptor 1A (5-HT1A) receptors' activation has been reported to play a crucial role in managing neurological outcomes in the brain and other health disorders. This study aimed to investigate the role of aripiprazole, a dopamine D2 and 5-HT1A selective receptors' activator, in the restoration of memory deficit induced by streptozotocin in mice. The cognitive functions of animals were determined using the Morris water maze. Brain sections were stained with hematoxylin and eosin and Congo red to examine the structural deviations. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), acetylcholinesterase activity, IL-6, and IL-10 were measured to assess biochemical alterations. Activation of D2 and 5-HT1A with aripiprazole attenuated STZ-induced cognitive deficit, increased brain GSH levels, reduced TBARS levels, AChE activity, IL-6 levels, and IL-10 levels and prevented STZ-induced brain anomalies in mice. Hence, the present study concluded that aripiprazole mitigated STZ-induced memory impairment and can be used as an efficacious therapeutic target for the management of AD.

Mechanistic insights into the role of plant polyphenols and their nano-formulations in the management of depression.

Depression is a condition characterized by low mood and an aversion to activity, that causes behavioral problems, poor quality of life and limits daily life activities. It is considered as the fourth leading cause of disability worldwide. Selective Serotonin Reuptake Inhibitors (SSRIs) Monoamine Oxidase (MAO) inhibitors, Tricyclic Antidepressants (TCAs), and atypical antidepressants are some of the conventional medications used to treat depression. However, only about half of patients with major depressive disorder (MDD) respond effectively to first-line antidepressant therapy. Additionally, there are a number of drawbacks to standard antidepressants, such as anti-cholinergic side effects, drug-drug interactions, and food-drug interactions, which prompts researchers to look at alternative approaches to the treatment of depression. Medicinal plants and their metabolites are extensively tested for their efficacy against depression. Electronic databases such as Google scholar, Science Direct, SciFinder and PubMed were used to search relevant literature on the role of polyphenols in depression. Plants-derived Polyphenols represent a major class of compounds extensively distributed in plants. Number of polyphenols have demonstrated antidepressant activity, among which berberine, piperine, curcumin, naringenin, ascorbic acid and ginsenosides are extensively evaluated. The medicinal plants and their derived compounds mediated synthesized green nanoparticles have also exhibited considerable efficacy in the management of depression. The therapeutic effects of these phytochemicals is mediated via differentiation and inhibition of neuronal cell apoptosis, promotion of neuronal cell survival and modulation of key neurotransmitters. The aim of this study is to review compressively the chemical, pharmacological and neurological evidence showing the potential of polyphenols in depression.

Herbal Arsenal against Skin Ailments: A Review Supported by In Silico Molecular Docking Studies.

Maintaining healthy skin is important for a healthy body. At present, skin diseases are numerous, representing a major health problem affecting all ages from neonates to the elderly worldwide. Many people may develop diseases that affect the skin, including cancer, herpes, and cellulitis. Long-term conventional treatment creates complicated disorders in vital organs of the body. It also imposes socioeconomic burdens on patients. Natural treatment is cheap and claimed to be safe. The use of plants is as old as mankind. Many medicinal plants and their parts are frequently used to treat these diseases, and they are also suitable raw materials for the production of new synthetic agents. A review of some plant families, viz., Fabaceae, Asteraceae, Lamiaceae, etc., used in the treatment of skin diseases is provided with their most common compounds and in silico studies that summarize the recent data that have been collected in this area.

Cardioprotective Activity of Cassia fistula L. Bark Extract in Isoproterenol-Induced Myocardial Infarction Rat Model.

Cassia fistula Linn, generally recognized as Indian laburnum, is one of the ancient trees in the Indian subcontinent used for its ornamental and diverse medicinal properties. It is known for its ethnic medicinal uses in inflammatory and infectious pathologies such as antihelmintic, purgative, carminative, antipyretic, expectorant, analgesic, laxative, antiseptic, and antidote against snake poison. The Cassia bark is rich in anthraquinones, flavanols glycosides, and sitosterols, which renders it cardioprotective properties. The existing experiments were designed to assess the potential of Cassia fistula bark against isoproterenol (ISP)-induced cardiotoxicity in rats, which has not been validated yet. The bark was successively extracted with five different solvents, and each extract was subjected to in vitro antioxidant studies. Further acute oral toxicity assays were carried out preceding in vivo myocardial studies. Cardiotoxicity-inducing agent, ISP, was administrated to the rats for two consecutive days (8th and 9th). Based on in vitro studies, the Cassia fistula methanolic extract (CFME) was administered in two doses: CFME-LD (lower dose 250 mg/kg) and CFME-HD (high dose 500 mg/kg) separately. It was found that CFME produced a substantial decrease in lipid peroxidation and an increase in antioxidants in myocardial tissues. CFME abrogated the levels of triglyceride and total cholesterol with a decrease in alanine transaminase (ALT) and aspartate transaminase (AST) activity in serum at both doses. 2,3,5-Triphenyltetrazolium chloride (TTC) staining and histopathology also revealed the protective effects of CFME against ISP-induced myocardial infarction. The study showed the significant role of the CFME as a strong antioxidant and cardioprotective action in ISP-induced toxicity.

In Silico and In Vitro Screening Constituents of Eclipta alba Leaf Extract to Reveal Antimicrobial Potential.

Phytochemicals have been shown to possess multiple bioactives and have been reported to showcase many medicinal effects. A similar kind of evaluation of phytoconstituents for their antimicrobial action has been reported, based on in vitro and in silico data. The goal of the research was to explore bioactive phytoconstituents of Eclipta alba leaf for antimicrobial activity. The antimicrobial activity was validated by both molecular docking and antimicrobial assay. Bioactive metabolites were identified using GC-MS. The antimicrobial and antimycobacterial activity of Eclipta alba leaves was investigated using the Kirby-Bauer well diffusion method and the rapid culture-MGIT™ DST method against a variety of human pathogens, as well as Mycobacterium tuberculosis (H37Rv) and Mycobacterium tuberculosis bacteria resistant to isoniazid and rifampicin. Eclipta alba's GC-MS studies confirmed the detection of 17 bioactive constituents. The extract demonstrates the highest antibacterial activity against Escherichia coli (sensitive), Pseudomonas aeruginosa (sensitive) and methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa susceptible and MRSA (sensitive) with zone of inhibition of 27 mm, 24 mm, and 32 mm respectively. The extract showed no effect on Mycobacterium tuberculosis (H37Rv) and Mycobacterium tuberculosis bacteria resistant to isoniazid and rifampicin in antimycobacterial activity testing. Molecular docking investigation revealed that three compounds (phthalic acid, isobutyl octadecyl ester, hexadecanoic acid, 1(hydroxymethyl)1,2-ethanediylester, and 2,myristynoyl pantetheine) have generated the best results in terms of binding energies and significant interactions with key residues of target protein 3-hydroxydecanoyl-acyl carrier protein dehydratase (FabA) and confirm its activity as antimicrobial inhibitors. These two-dimensional plots show significant protein-ligand binding interactions (van der Waals interactions, hydrogen bond, alkyl, and Pi-alkyl interactions). ADMET (absorption, distribution, metabolism, excretion, and toxicity) results additionally support the drug-likeness characteristics of concluded potential compounds. The experimental and computational results demonstrated that methanolic extract of Eclipta alba leaves had antimicrobial effects for specific infections due to the presence of phytochemical compounds.

Identification of Novel and Safe Fungicidal Molecules against Fusarium oxysporum from Plant Essential Oils: In Vitro and Computational Approaches.

Phytopathogenic fungi are serious threats in the agriculture sector especially in fruit and vegetable production. The use of plant essential oil as antifungal agents has been in practice from many years. Plant essential oils (PEOs) of Cuminum cyminum, Trachyspermum ammi, Azadirachta indica, Syzygium aromaticum, Moringa oleifera, Mentha spicata, Eucalyptus grandis, Allium sativum, and Citrus sinensis were tested against Fusarium oxysporum. Three phase trials consist of lab testing (MIC and MFC), field testing (seed treatment and foliar spray), and computer-aided fungicide design (CAFD). Two concentrations (25 and 50 µl/ml) have been used to asses MIC while MFC was assessed at four concentrations (25, 50, 75, and 100 µl/ml). C. sinensis showed the largest inhibition zone (47.5 and 46.3 m2) for both concentrations. The lowest disease incidence and disease severity were recorded in treatments with C. sinensis PEO. Citrus sinensis that qualified in laboratory and field trials was selected for CAFD. The chemical compounds of C. sinensis PEO were docked with polyketide synthase beta-ketoacyl synthase domain of F. oxysporum by AutoDock Vina. The best docked complex was formed by nootkatone with -6.0 kcal/mol binding affinity. Pharmacophore of the top seven C. sinensis PEO compounds was used for merged pharmacophore generation. The best pharmacophore model with 0.8492 score was screened against the CMNP database. Top hit compounds from screening were selected and docked with polyketide synthase beta-ketoacyl synthase domain. Four compounds with the highest binding affinity and hydrogen bonding were selected for confirmation of lead molecule by doing MD simulation. The polyketide synthase-CMNPD24498 showed the highest stability throughout 80 ns run of MD simulation. CMNPD24498 (FW054-1) from Verrucosispora was selected as the lead compound against F. oxysporum.

Fruit and Vegetable Peel-Enriched Functional Foods: Potential Avenues and Health Perspectives.

Fresh fruit and vegetables are highly utilized commodities by health-conscious consumers and represent a prominent segment in the functional and nutritional food sector. However, food processing is causing significant loss of nutritional components, and the generation of waste is creating serious economic and environmental problems. Fruit and vegetables encompass husk, peels, pods, pomace, seeds, and stems, which are usually discarded, despite being known to contain potentially beneficial compounds, such as carotenoids, dietary fibers, enzymes, and polyphenols. The emerging interest in the food industry in the nutritional and biofunctional constituents of polyphenols has prompted the utilization of fruit and vegetable waste for developing enriched and functional foods, with applications in the pharmaceutical industry. Moreover, the utilization of waste for developing diverse and crucial bioactive commodities is a fundamental step in sustainable development. Furthermore, it provides evidence regarding the applicability of fruit and vegetable waste in different food formulations especially bakery, jam, and meat based products.

Identification of Effective and Nonpromiscuous Antidiabetic Drug Molecules from Penicillium Species.

Diabetes mellitus (DM) is a very common metabolic disorder/disease. The deterioration of ß-cells by autoimmune system is the hallmark of this disease. Thioredoxin-Interacting Protein (TXNIP) is responsible for ß-cells degradation by T-cells in the pancreas. This protein had been declared a good drug target for controlling DM. Lots of side effects have been reported as a result of long-time consumption of conventional antidiabetic drugs. The development of new and effective drugs with the minimal side effects needs time. TXNIP was selected as a target for Computer-Aided Drug Design. The antidiabetic fungal metabolite compounds were selected from the literature. The compounds were screened for their drug-likeness properties by DruLiTo and DataWarior tools. Twenty-two drug-like fungal compounds were subjected to Quantitative Structure-Activity Relationship (QSAR) analysis by using CheS-Mapper 2.0. The lowest (0.01) activity cliff was found for three compounds: Pinazaphilone A, Pinazaphilone B, and Chermesinone A. The highest value for apol (81.76) was shown by Asperphenamate, while Albonoursin and Sterenin L showed highest score (40.66) for bpol. The lowest value (0.46) for fractional molecular frame (FMF) was calculated for Pinazaphilone A and Pinazaphilone B. TPSA for Pinazaphilone A and Pinazaphilone B was 130.51 Å2. log P < 5 was observed for all the twenty-two compounds. Molecular docking of fungal compounds with TXNIP was done by AutoDock Vina. The binding energy for complexes ranged between -9.2 and -4.6 kcal/mol. Four complexes, TXNIP-Pinazaphilone A, TXNIP-Pinazaphilone B, TXNIP-Asperphenamate, and TXNIP-Sterenin L, were selected for MD simulation to find out the best lead molecule. Only one complex, TXNIP-Pinazaphilone B, showed a stable conformation throughout the 80 ns run of MD simulation. Pinazaphilone B derived from the Penicillium species fungi was selected as the lead molecule for development of antidiabetic drug having the least side effects.

Cardioprotection by Citrus grandis (L.) Peel Ethanolic Extract in Alloxan-Induced Cardiotoxicity in Diabetic Rats.

Diabetic cardiomyopathy (DCM) pathogenesis is multifarious, and there are insufficient therapeutic options to treat DCM. The present research explored the effects of Citrus grandis peel ethanolic extract (CGPE) in alloxan-induced DCM in rats. Diabetes was triggered by intraperitoneal (i.p.) injection of alloxan (150 mg/kg) in Wistar rats (200-250 g). CGPE (100, 200, and 400 mg/kg) or glibenclamide (Glib, 10 mg/kg) were administered orally for 2 weeks. After the treatment schedule, prooxidants (thiobarbituric acid reactive substances), antioxidants (glutathione, catalase, and superoxide dismutase), and inflammatory markers (tumor necrosis factor-α) were determined in cardiac tissues. Biomarkers of cell death, viz., lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) activity, glucose levels, total cholesterol (TC), and high-density lipoproteins (HDL), were assessed in the blood. Rats administered with alloxan showed a consistent increase in blood glucose level (days 7 and 14) that was lowered considerably (p < 0.001) by CGPE or Glib. Alloxan-induced increase in LDH, CK-MB, TC, and decline in HDL was attenuated (p < 0.001) in rats that were treated with CGPE or Glib. Alloxan significantly (p < 0.001) elevated oxidative stress, inflammation, and reduced antioxidants in the cardiac tissue of rats, and these pathogenic abnormalities were ameliorated (p < 0.001) by CGPE. Histopathological studies showed a decrease in morphological disruptions by alloxan in CGPE-treated rats. CGPE (400 mg/kg) significantly ameliorated biochemical parameters in comparison to the lower doses against alloxan cardiotoxicity. Citrus grandis peel extract can be an alternative in the management of DCM.

Isolation of Thymol from Trachyspermum ammi Fruits for Treatment of Diabetes and Diabetic Neuropathy in STZ-Induced Rats.

Terpenoids and phenols from Trachyspermum ammi (T. ammi) have reported some pharmacological actions. The objective of the work was to isolate the active constituent, its identification by spectroscopic techniques, and evaluation of the antidiabetic and neuroprotective activity from T. ammi on STZ Wistar rats. The dried fruits of T ammi were kept in a hydrodistillation apparatus to collect essential oil. The isolated fraction went through TLC, UV, FTIR, HPLC, HRMS, C13, and 1H NMR for characterization. Two dosage concentrations from the isolated compound were prepared as 10 and 20 mg/kg for treatment groups. The groups were tested for thermal and mechanical hyperalgesia, writhing, grip strength, spontaneous locomotor test, neuromuscular coordination tests, and histopathological and lipid profile analysis. Diabetes was induced by streptozotocin (45 mg/kg i.p.) and 12 weeks of treatment-induced diabetic neuropathy in Wistar rats. Biomarkers were evaluated to understand the neuropathic protection of thymol on STZ-treated Wistar rats. The biomarker studies (SOD, NO, LPO, Na+K+ATPase, and TNF-α) further confirmed thymol's diabetic neuropathy protective action. This study suggests that isolated compound thymol was antidiabetic and neuroprotective as it has shown controlled glucose levels defensive nerve damage in STZ Wistar rats. P < 0.05 level of significance was observed in the levels of endogenous biomarkers, fasting blood glucose levels, actophotometer response, and response latency in treated groups compared to the diabetic group, whereas P < 0.001 level of significance during lipid profile levels, thermal algesia, and neuromuscular comparison tests was noted in treated groups compared to the diabetic group.

Antioxidant, Enzyme Inhibitory, and Molecular Docking Approaches to the Antidiabetic Potentials of Bioactive Compounds from Persicaria hydropiper L.

Introduction: Natural products are among the most useful sources for the discovery of new drugs against various diseases. Keeping in view the ethnobotanical relevance ethnopharmacological significance of Polygonaceae family in diabetes, the current study was designed to isolate pure compounds from Persicaria hydropiper L. leaves and evaluate their in vitro and in silico antidiabetic potentials. Methods: Six compounds were isolated from the chloroform-ethyl acetate fractions using gravity column chromatography and were subjected to structure elucidation process. Structures were confirmed using 1H-NMR, 13C-NMR, and mass spectrometry techniques. Isolated phytochemicals were subjected to in vitro antidiabetic studies, including α-glucosidase, α-amylase inhibition, and DPPH, and ABTS antioxidant studies. Furthermore, the in silico binding mode of these compounds in the target enzymes was elucidated via MOE-Dock software. Results: The isolated compounds revealed concentration-dependent inhibitions against α-glucosidase enzyme. Ph-1 and Ph-2 were most potent with 81.84 and 78.79% enzyme inhibitions at 1000 µg·mL-1, respectively. Ph-1 and Ph-2 exhibited IC50s of 85 and 170 µg·mL-1 correspondingly. Likewise, test compounds showed considerable α-amylase inhibitions with Ph-1 and Ph-2 being the most potent. Tested compounds exhibited considerable antioxidant potentials in both DPPH and ABTS assays. Molecular simulation studies also revealed top-ranked confirmations for the majority of the compounds in the target enzymes. Highest observed potent compound was Ph-1 with docking score of -12.4286 and formed eight hydrogen bonds and three H-pi linkages with the Asp 68, Phe 157, Phe 177, Asn 241, Glu 276, His 279, Phe 300, Glu 304, Ser 308, Pro 309, Phe 310, Asp 349, and Arg 439 residues of α-glucosidase binding packets. Asp 68, Glu 276, Asp 349, and Arg 439 formed polar bonds with the 3-ethyl-2-methylpentane moiety of the ligand. Conclusions: The isolated compounds exhibited considerable antioxidant and inhibitory potentials against vital enzymes implicated in T2DM. The docking scores of the compounds revealed that they exhibit affinity for binding with target ligands. The enzyme inhibition and antioxidant potential of the compounds might contribute to the hypoglycemic effects of the plant and need further studies.