Multi-target mechanism of Solanum xanthocarpum for treatment of psoriasis based on network pharmacology and molecular docking.

Solanum xanthocarpum (SX) has been used to treat a variety of diseases, including skin disorders like psoriasis (PSO). SX possesses many pharmacological activities of anti-inflammatory, anti-cancer, immunosuppressive, and healing qualities. However, the multi-target mechanism of SX on PSO still needs clarity. Materials and methods: The Indian Medicinal Plants, Phytochemicals and Therapeutics (IMPPAT) database and the Swiss Target Prediction online tool were used to find the active phytochemical components and their associated target proteins. OMIM and GeneCards databases were used to extract PSO-related targets. A Venn diagram analysis determined the common targets of SX against PSO. Subsequently, the protein-protein interaction (PPI) network and core PPI target analysis were carried out using the STRING network and Cytoscape software. Also, utilising the online Metascape and bioinformatics platform tool, a pathway enrichment analysis of common targets using the Kyoto Encyclopaedia of Genes and Genome (KEGG) and Gene Ontology (GO) databases was conducted to verify the role of targets in biological processes, cellular components and molecular functions with respect to KEGG pathways. Lastly, molecular docking simulations were performed to validate the strong affinity between components of SX and key target receptors. Results: According to the IMPPAT Database information, 8 active SX against PSO components were active. According to the PPI network and core targets study, the main targets against PSO were EGFR, SRC, STAT3, ERBB2, PTK2, SYK, EP300, CBL, TP53, and AR. Moreover, molecular docking simulations verified the binding interaction of phytochemical SX components with their PSO targets. Last but not least, enrichment analysis showed that SX is involved in several biological processes, including peptidyl-tyrosine phosphorylation, peptidyl-tyrosine modification, and peptidyl-serine modification. The relevant KEGG signalling pathways are the PI3K-AKT signalling pathway, the EGFR tyrosine kinase inhibitor resistance pathway, and the MAPK signalling pathway. Conclusion: The network pharmacology technique, which is based on data interpretation and molecular docking simulation techniques, has proven the multi-target function of SX phytoconstituents.

In-vitro and ex-vivo antidiabetic, and antioxidant activities of Box-Behnken design optimized Solanum xanthocarpum extract loaded niosomes.

One of the most prevalent lifestyle diseases, diabetes mellitus (DM) is brought on by an endocrine issue. DM is frequently accompanied by hyperglycemia, a disease that typically results in an excess of free radicals that stress tissues. The medical community is currently concentrating on creating therapeutic medications with roots in nature to lessen the damage associated with hyperglycemia. Solanum xanthocarpum has a number of medicinal benefits. The investigation aimed to produce and analyze niosomal formulations containing S. xanthocarpum extract (SXE). Niosomes were made by implementing the solvent evaporation process, which was further optimized using Box-Behnken design. Drug release, DPPH assessments, α-amylase inhibition assay, α-glucosidase inhibition assay, and confocal laser scanning microscopy (CLSM) investigation were all performed on the developed formulation (SXE-Ns-Opt). SXE-Ns-Opt displayed a 253.6 nm vesicle size, a PDI of 0.108, 62.4% entrapment efficiency, and 84.01% drug release in 24 h. The rat's intestinal CLSM image indicated that the rhodamine red B-loaded SXE-Ns-Opts had more intestinal penetration than the control. Additionally, the antioxidant effect of the obtained formulation was demonstrated as 89.46% as compared to SXE (78.10%). Additionally, acarbose, SXE, and SXE-Ns-Opt each inhibited the activity of α-amylase by 95.11%, 85.88%, and 89.87%, and also suppressed the enzyme of α-glucosidase by 88.47%, 81.07%, and 85.78%, respectively. To summarise, the establishment of the SXE-Ns-Opt formulation and its characterization demonstrated the legitimacy of the foundation. A promising candidate for the treatment of diabetes mellitus has been shown as in vitro studies, antioxidant against oxidative stress, CLSM of rat's intestine and a high degree of penetration of formulation.

Preclinical assessment of stem of Nicotiana tabacum on excision wound model.

Agro-waste material derived from N. tabacum has shown enormous potential antioxidant and antimicrobial activity. Hence in the present study, we investigated the wound healing efficacy of ethanolic extract of stem of Nicotiana tabacum on wistar rat model. Ethanolic extract prepared from defatted stem was to check various phytochemicals using spectrophotometric and chromatographic technique. The antioxidant potential was determined by FRAP and Reducing Power assay in extract. Cytotoxicity of extracts was determined using mouse fibroblast L929 cell lines by MTT assay. In vivo angiogenic activity was observed on chick chorioallantoic membrane (CAM) model by observing blood vessels formation and its branching. In vivo wound healing activity was observed on excision wounds in rat model by quantifying percentage of wound contraction, antioxidant activity and histopathology studies. From the present study, polyphenols, tannins and alkaloids were found to be determined in the ethanolic extract by means of spectrophotometric and chromatographic analysis against standards. Antioxidant assay revealed maximum antioxidant potential in ethanolic extract. Cytotoxic effect of extract has not been shown on L929 cell line. From CAM model, extract has shown growth of blood vessels formation at concentration of 480 µg/ml. Topical application of extracts on excision wounds, revealed wound healing activity i.e. 98.7% ± 0.002 on 14th day as well as enzymatic activity (SOD, CAT, GST) and non enzyme content (GSH and Lipid peroxidation) has been found to be high in granulated tissue. Hisopathological studies confirmed the re-epithelization in skin wounds. It can be concluded that stem of N. tabacum can be used as herbal remedy in wound healing process as a topical application.

Acanthosis nigricans independently predicts hepatic fibrosis in people with type 2 diabetes in North India.

BACKGROUND: Acanthosis nigricans (AN) is a skin condition characterized by hyperpigmentation and thickening, often found in individuals with insulin resistance. Despite this well-established association, the potential link between AN and hepatic fibrosis in people with type 2 diabetes (T2D) has yet to be thoroughly explored. METHODOLOGY: We recruited a total of 300 people with T2D, half of whom had AN (n, 150), and the other half without AN (n, 150). We evaluated body composition, biochemistry, and hepatic fat analysis (using the controlled attenuation parameter, CAP), as well as assessments of hepatic stiffness (using the kilopascal, kPa) using Fibroscan. We used multivariable regression analysis to find independent predictors of AN and their relationship to hepatic fibrosis. Furthermore, we developed a prediction equation and AUC for hepatic fibrosis. RESULTS: Upon comparison between AN vs. NAN group, following were significatly higher; weight, BMI, hepatic transaminases, liver span, CAP, and kPa. After adjusting for age, weight, body mass index, diabetes duration, and specific anti-hyperglycaemic drugs (gliclazide, DPP-4 inhibitors, pioglitazone, and Glucagon-like peptide-1 receptor agonists), adjusted OR for AN were, liver span, 1.78 (95% CI: 0.91-3.49, p = 0.09), CAP, 7.55 (95% CI: 0.93-61.1, p = 0.05), and kPa, 2.47 (95% CI: 1.50-4.06, p = 0.001). A ROC analysis of predictive score for hepatic fibrosis showed optimal sensitivity and specificity at a score cut-off of 25.2 (sensitivity 62%, specificity 63%), with an AUC of 0.6452 (95% CI: 0.61235-0.76420). CONCLUSION: Acanthosis nigricans has the potential to be used as an easy-to-identify clinical marker for risk of hepatic fat and fibrosis in Asian Indians with T2D, allowing for early detection and management strategies.

Optimization, In Vitro and Ex Vivo Assessment of Nanotransferosome Gels Infused with a Methanolic Extract of Solanum xanthocarpum for the Topical Treatment of Psoriasis.

The goal of this investigation is to improve the topical delivery of medicine by preparing and maximizing the potential of a nanotransferosome gel infused with Solanum xanthocarpum methanolic extract (SXE) to provide localized and regulated distribution. Thin-film hydration was used to create SXE-infused nanotransferosomes (SXE-NTFs), and a Box-Behnken design was used to improve them. Phospholipon 90G (X1), cholesterol (X2) and sodium cholate (X3) were chosen as the independent variables, and their effects on vesicle size (Y1), polydispersity index (PDI) (Y2) and the percentage of entrapment efficiency (EE) (Y3) were observed both individually and in combination. For the SXE-NTFs, the vesicle size was 146.3 nm, the PDI was 0.2594, the EE was 82.24 ± 2.64%, the drug-loading capacity was 8.367 ± 0.07% and the drug release rate was 78.86 ± 5.24%. Comparing the antioxidant activity to conventional ascorbic acid, it was determined to be 83.51 ± 3.27%. Ex vivo permeation tests revealed that the SXE-NTF gel (82.86 ± 2.38%) considerably outperformed the SXE gel (35.28 ± 1.62%) in terms of permeation. In addition, it seemed from the confocal laser scanning microscopy (CLSM) picture of the Wistar rat's skin that the rhodamine-B-loaded SXE-NTF gel had a higher penetration capability than the control. Dermatokinetic studies showed that the SXE-NTF gel had a better retention capability than the SXE gel. According to the experimental results, the SXE-NTF gel is a promising and successful topical delivery formulation.

Sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus and moderate to severe hepatic fibrosis: A retrospective study.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to decrease hepatic transaminases, steatosis, and in some studies, hepatic fibrosis. However, the safety and efficacy of SGLT2i has not been tested in patients who have moderate to severe hepatic fibrosis. METHODS: In a retrospective study of sixty patients with moderate to severe hepatic fibrosis (kPa estimated by Fibroscan > 10), SGLT2i were prescribed on top of other oral anti-hyperglycemic medications. The safety and efficacy of SGLT2i were evaluated. Using the Fibroscan, CAP scores (decibel/meter), and liver stiffness measurement (LSM) (kPa, kilopascals) were examined before and after treatment. RESULTS: The mean age of the T2DM patients was 54.7 ± 10.3 years, and the mean duration of T2DM was 8.3 ± 7.1 years. SGLT2i were given from 3 to 36 months. After treatment, a decrease in glycated hemoglobin (HbA1c), and hepatic transaminases (SGOT and SGPT) was recorded. Upon follow up, CAP and kPa scores decreased significantly. Importantly, no adverse drug reaction, such as balanoposthitis, vulvovaginitis, urosepsis, and postural drop in blood pressure, were reported in any patient. CONCLUSION: In this retrospective cohort study, patient with T2DM and moderate to severe hepatic fibrosis, use of SGLT2i is safe with respect to common adverse effects & may have contributed to improved hepatic profile.

Formulation and Evaluation of Plumbagin-Loaded Niosomes for an Antidiabetic Study: Optimization and In Vitro Evaluation.

Diabetes treatment requires focused administration with quality systemic circulation to determine the optimal therapeutic window. Intestinal distribution through oral administration with nanoformulation provides several benefits. Therefore, the purpose of this study is to create plumbagin enclosed within niosomes using the quality by design (QbD) strategy for efficient penetration and increased bioavailability. The formulation and optimization of plumbagin-loaded niosomes (P-Ns-Opt) involved the use of a Box-Behnken Design. The particle size (PDI) and entrapment efficiency of the optimized P-Ns-Opt were 133.6 nm, 0.150, and 75.6%, respectively. TEM, DSC, and FTIR were used to analyze the morphology and compatibility of the optimized P-Ns-Opt. Studies conducted in vitro revealed a controlled release system. P-Ns-Opt's antioxidant activity, α-amylase, and α-glucosidase were evaluated, and the results revealed a dose-dependent efficacy with 60.68 ± 0.02%,90.69 ± 2.9%, and 88.43 ± 0.89%, respectively. In summary, the created P-Ns-Opt demonstrate remarkable potential for antidiabetic activity by inhibiting oxygen radicals, α-amylase, and α-glucosidase enzymes and are, therefore, a promising drug delivery nanocarrier in the management and treatment of diabetes.

Single and repeated dose (28 days) intravenous toxicity assessment of bartogenic acid (an active pentacyclic triterpenoid) isolated from Barringtonia racemosa (L.) fruits in mice.

Bartogenic acid (BA), an active pentacyclic triterpenoid, has been reported for anti-diabetic, anti-inflammatory, anti-arthritic, anti-cancer, and anti-tumor activity. However, toxicity profiling of BA has not been reported till date. Hence, this study is designed to evaluate the single dose (12.5, 25, 50 and 100 mg/kg) and repeated dose (1.5, 6, and 24 mg/kg) intravenous toxicity of BA in BALB/c mice. Control group received vehicle. In single dose toxicity study, two mortalities were observed at 100 mg/kg of BA whereas lower doses were well tolerated. In repeated dose toxicity study, no mortality was observed. 1.5 mg/kg of BA was well tolerated in mice of both sexes. At 6 mg/kg of BA, female mice showed significant reduction in the body weight as compared to the control group however no significant change was observed in male mice. 24 mg/kg of BA showed significant reduction in the body weight in mice of both sexes. Further, these mice showed significant change in the relative organ weight. However, no toxicologically relevant changes were observed in hematology, biochemistry, and histopathology. Based on the findings, No-Observed-Adverse-Effect-Level (NOAEL) for BA were found to be<24 mg/kg for male mice and<6 mg/kg for female mice.

Effect of Multimodal Intervention (computer based cognitive training, diet and exercise) in comparison to health awareness among older adults with Subjective Cognitive Impairment (MISCI-Trial)-A Pilot Randomized Control Trial.

INTRODUCTION: This study was aimed to investigate the effect of multimodal intervention on the cognitive functions of older adults with subjective cognitive impairment (SCI). MATERIALS AND METHODS: Sixty subjects were randomized 1:1:1:1 to receive either computer based cognitive therapy (CBCT) or CBCT+Mediterranean equivalent diet (MED) or CBCT+MED+ Exercise regime and the control group. The intervention group received supervised CBCT twice a week to have 40 sessions, each of 40 minutes duration, and/ or supervised aerobic and resistive exercise twice a week for 24 weeks and or MED at home under the supervision of a dietician. The control group was provided with health awareness instructions for brain stimulating activities such as sudoku, mental maths, and learning music and new skills. RESULTS: Cognitive functions which was the primary outcome measure were assessed using the Post Graduate Institute Memory Scale (PGI-MS), and Stroop Colour and Word Test at baseline and after 6 months intervention period. As assessed by the PGI-MS, there was significant improvement in domains such as mental balance, attention and concentration, delayed recall, immediate recall, verbal retention of dissimilar pairs, Visual retention, and total score both in the unimodal and multimodal intervention groups. However, the improvement was observed to be the highest in the multimodal intervention group as compared to unimodal group. All the participants completed the trial. CONCLUSION: This pilot randomized control trial indicated that multimodal intervention could be an effective non-pharmacological intervention in individuals with SCI for improving their cognitive functions.

Antiurolithic efficacy of a phenolic rich ethyl acetate fraction of the aerial parts of Aerva lanata (Linn) Juss. ex Schult. in ethylene glycol induced urolithic rats.

OBJECTIVES: The study was carried out to evaluate the in vivo antiurolithic efficaciousness of an ethyl acetate fraction of Aerva lanata (EAFAL) derived from the hydromethanolic extract of its aerial parts (HMEAL). METHODS: In vivo pharmacological potency of EAFAL was assessed by ethylene glycol (EG) induced urolithiasis model in male Wistar albino rats. Urine samples of the animals were analysed for physical parameters, stone promoters, inhibitors along with an evaluation of the biochemical parameters of serum and kidneys. Histopathological investigation of the kidneys was done. The fraction was further subjected to LC-MS and HPLC for its phytochemical evaluation. KEY FINDINGS: EAFAL demonstrated a significant antiurolithic effect by a restoration of the balance between urinary promoters and inhibitors along with an amelioration of the urinary pH. The abnormally elevated levels of serum nitrogenous substances, calcium, albumin, globulin, total protein along with altered renal calcium, oxalate and uric acid were also alleviated significantly followed by an improvement of the histopathological aberrancies. Phytochemical analysis showed evidence of phenolic components and flavonoids. CONCLUSIONS: The current findings prove the beneficial role of phenolic and flavonoid rich EAFAL in ameliorating urolithiasis induced abnormalities of urine, serum and kidneys.

SIRT1 Promotes Neuronal Fortification in Neurodegenerative Diseases through Attenuation of Pathological Hallmarks and Enhancement of Cellular Lifespan.

Neurodegeneration is a complex neurological phenomenon characterized by disturbed coherence in neuronal efflux. Progressive neuronal loss and brain damage due to various age-related pathological hallmarks perturb the behavioral balance and quality of life. Sirtuins have been widely investigated for their neuroprotective role, with SIRT1 being the most contemplated member of the family. SIRT1 exhibits significant capabilities to enhance neurogenesis and cellular lifespan by regulating various pathways, which makes it an exciting therapeutic target to inhibit neurodegenerative disease progression. SIRT1 mediated neuronal fortification involves modulation of molecular co-factors and biochemical pathways responsible for the induction and sustenance of pro-inflammatory and pro-oxidative environment in the cellular milieu. In this review, we present the major role played by SIRT1 in maintaining cellular strength through the regulation of genomic stability, neuronal growth, energy metabolism, oxidative stress, inhibiting mechanisms and anti-inflammatory responses. The therapeutic significance of SIRT1 has been put into perspective through a comprehensive discussion about its ameliorating potential against neurodegenerative stimuli in a variety of diseases that characteristically impair cognition, memory and motor coordination. This review enhances the acquaintance concerned with the neuroprotective potential of SIRT1 and thus promotes the development of novel SIRT1 regulating therapeutic agents and strategies.

Isoflavonoids from Flemingia strobilifera (L) R. Br. roots.

A new isoflavone (1) isolated from the roots of Flemingia strobilifera (L) R. Br. was identified as 5,7,4'-trihydroxy 8,2',5'-tri(3-methylbut-2-enyl)isoflavone along with the known phytoconstituents: 5,7,2',4'-tetrahydroxyisoflavone (2), 5,7,4'-trihydroxyisoflavone (3) and beta-sitosterol (4). Structure assignments were performed on the basis of spectroscopic data including homo- and heteronuclear 1D and 2D NMR (COSY, HMBC and DEPT) and MS studies. The compounds were tested in vitro for antimicrobial activity and antioxidant activity and compounds (1-3) proved to be moderately active.

Phenolic glucosides from Flacourtia indica.

A new phenolic glucoside, (rel)-2-(4',6' -dibenzoyl-beta-glucopyranosyloxy)-7-(1alpha-hydroxy-2alpha-ethoxy-6alpha-acetyloxy-3-oxocyclohex-4-enoyl)-benzyl alcohol (Flacourticin) (1) and the known, 2-(4',6'-dibenzoyl-beta-glucopyranosyl)-5-hydroxy benzyl alcohol (4'-benzoylpoliothrysoside) (2) together with the new, (2E)-heptyl-3-(3,4-dihydroxyphenyl) acrylate (3), (+)-catechin (4) and sitosterol-beta-D-glucoside were isolated from Flacourtia indica. Their structures were assigned on the basis of 1D, 2D-NMR and as well by analysis of the LC-ESIMS data. The isolated compounds (1-4) were evaluated for alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical scavenging activity, and 3 was found to be two-fold less potent, with an IC50 = 12.01 microg/mL, compared to the positive control, Rutin, (IC50 = 5.83 microg/mL).