Exploring non-cytotoxic, antioxidant, and anti-inflammatory properties of selenium nanoparticles synthesized from Gymnema sylvestre and Cinnamon cassia extracts for herbal nanomedicine.

The increasing need for pharmaceutical agents that possess attributes such as safety, cost-effectiveness, environmental sustainability, and absence of side effects has driven the advancement of nanomedicine research, which lies at the convergence of nanotechnology and medicine. AIMS AND OBJECTIVES: The study aimed to synthesize non-toxic selenium nanoparticles (SeNPs) using Gymnema sylvestre (G. sylvestre) and Cinnamon cassia (C. cassia) extracts. It also sought to develop and evaluate versatile nanomedicine formulations i.e. selenium nanoparticles of G. sylvestre and C. cassia (SeNPs), drug (lupeol) loaded SeNPs (DLSeNPs), drug-loaded and coated (PEG) SeNPs (DLCSeNPs) without side effects. METHODS: The SeNPs formulations were hydrothermally synthesized, loaded with lupeol to improve efficacy, coated with polyethylene glycol (PEG) for targeted delivery, and characterized using UV-Vis spectrophotometry, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), zeta potential analysis, size distribution analysis, and X-ray diffraction (XRD). Hemolytic cytotoxicity, 2,2-Diphenyl-1-picrylhydzayl (DPPH), total Reducing power, and total antioxidant capacity (TAC) antioxidant assays, carrageenan-induced paw edema, and histological studies were used to estimate the acute anti-inflammatory activity of the synthesized SeNPs. RESULTS: The final form of PEGylated and drug (lupeol)-loaded selenium nanoparticles (DLCSeNPs) exhibited an average particle size ranging from 100 to 500 nm as evidenced by SEM, and Zeta potential results. These nanoparticles demonstrated no cytotoxic effects and displayed remarkable antioxidant (IC50 values 19.29) and anti-inflammatory capabilities. These results were fed into Graph-pad Prism 5 software and analyzed by one-way ANOVA, followed by Tukey's post hoc test (p < 0.001). All nano-formulations exhibited significant overall antioxidant activity, with IC50 values ≤ 386 (p < 0.05) as analyzed by ANOVA. The study's results suggest that G. sylvestre outperformed C. cassia in terms of reducing 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical, potassium ferricyanide, and ammonium molybdate in respective antioxidant assays. As far as anti-inflammatory activities are concerned drug (lupeol)-loaded and PEG-coated G. sylvestre SeNPs exhibited the highest anti-inflammatory potential from all other nano-formulations including drug (lupeol)-loaded and PEG-coated C. cassia SeNPs, as exhibited to reduce the release of pro-inflammatory signals i.e. cytokines and NF-kB, making them innovative anti-inflammatory nanomedicine. CONCLUSION: The study synthesized lupeol-loaded and PEG-coated SeNPs, showcasing the potential for biocompatible, cost-effective anti-inflammatory nanomedicines. G. Sylvester's superior antioxidant and anti-inflammatory performance than Cinnamon cassia emphasizes medicinal plant versatility.

Phytofabrication of biocompatible zinc oxide nanoparticle using Gymnema sylvestre and its potent in vitro antibacterial, antibiofilm, and cytotoxicity against human breast cancer cells (MDA-MB-231).

The increasing incidence of breast cancer and bacterial biofilm in medical devices significantly heightens global mortality and morbidity, challenging synthetic drugs. Consequently, greener-synthesized nanomaterials have emerged as a versatile alternative for various biomedical applications, offering new therapeutic avenues. This study explores the synthesis of biocompatible zinc oxide (ZnONPs) nanoparticles using Gymnema sylvestre and its antibacterial, antibiofilm, and cytotoxic properties. Characterization of ZnONPs inferred that UV-Vis spectra exhibited a sharp peak at 370 nm. Fourier transform infrared spectroscopical analysis revealed the presence of active functional groups such as aldehyde, alkyne, cyclic alkene, sulfate, alkyl aryl ether, and Zn-O bonds. X-ray diffraction analysis results confirmed the crystalline nature of the nanoparticle. Scanning electron microscope analysis evidenced hexagonal morphology, and energy-dispersive X-ray analysis confirmed zinc content. High-resolution transmission electron microscope analysis showed hexagonal and rod-shaped ZnONPs with a size of 5 nm. Zeta potential results affirmed the stability of nanoparticles. The ZnONPs effectively inhibited gram-positive (18-20 mm) than gram-negative (12-18 mm) bacterial pathogens with lower bacteriostatic and higher bactericidal values. Biofilm inhibitory property inferred ZnONPs were more effective against gram-positive (38-94%) than gram-negative bacteria (27-86%). The concentration of ZnONPs to exert 50% biofilm-inhibitory is lower against gram-positive bacteria (179.26-203.95 µg/mL) than gram-negative bacteria (201.46-236.19 µg/mL). Microscopic visualization inferred that at 250 µg/mL, ZnONPs strongly disrupted biofilm formation, as evidenced by decreased biofilm density and altered architecture. The cytotoxicity of ZnONPs against breast cancer cells showed a dose-dependent reduction in cell viability with an IC50 value of 19.4 µg/mL. AO/EB staining indicated early and late apoptotic cell death of breast cancer cells under fluorescence microscopy. The results of hemolytic activity validated the biocompatibility of the ZnONPs. Thus, the unique properties of the green-synthesized ZnONPs suggest their potential as effective drug carriers for targeted delivery in cancer therapy and the treatment of biofilm-related infections.

Biotechnological approaches for the production of gymnemic acid from Gymnema sylvestre R. Br.

Diabetes is a chronic disease that affects several organs and can be treated using phytochemicals found in medicinal plants. Gymnema sylvestre (Asclepiadaceae) is one such medicinal plant rich in anti-diabetic properties. The plant is commonly known as madhunashini in Sanskrit because of its ability to cure diabetes (sugar). Gymnemic acid (GA) is a phytochemical (a triterpenoid saponin) responsible for the herb's main pharmacological activity. This secondary metabolite has a lot of potential as a phytochemical with pharmacological properties including nephroprotection, hypoglycemia, antioxidant, antimicrobial, and anti-inflammatory. Gymnema has acquired a lot of popularity in recent years due to its low side effects and high efficacy in healing diabetes, which has led to overexploitation by pharmaceutical enterprises for its biomass in the wild for the purification of gymnemic acid. Modern biotechnological techniques involving the establishment of cell and organ cultures from G. sylvestre will assist us in fulfilling the need for gymnemic acid production. The present review provides insights on the establishment of cell and organ cultures for the production of a potent antidiabetic molecule gymnemic acid. Further, the review also delves into the intricacies of the different strategies for improved production of gymnemic acid using various elicitors. There is huge potential for sustainable production of gymnemic acid which could be met by establishment of bioreactor scale production. Understanding and engineering the biosynthetic pathway could also lead to improved GA production. KEY POINTS: • Gymnemic acid is one of the potential anti-diabetic molecules from madhunashini • Cell and organ culture offers potential approach for gymnemic acid production • Elicitation strategies have improved the gymnemic acid production.

The effects of Gymnema Sylvestre supplementation on lipid profile, glycemic control, blood pressure, and anthropometric indices in adults: A systematic review and meta-analysis.

There is a growing interest in the considerable health benefits of Gymnema Sylvestre (GS) supplementation, as some studies have reported that it may improve cardiometabolic risk factors. However, the widespread impact of GS supplementation on the parameters mentioned above is not fully resolved. Consequently, this study aimed to examine the effects of GS supplementation on lipid profile, glycemic control, blood pressure, and anthropometric indices in adults. Eligible randomized controlled trials (RCT), published up to November 2021, were identified through PubMed, Scopus, and ISI Web of Science databases. Six studies were included and analyzed using a random-effects model to calculate weighted mean differences (WMDs) with 95% confidence intervals (CI). All studies were conducted in adults that used a GC supplement (>1 week) and assessed our selected cardiovascular risk factors. Outcomes revealed that GS supplementation significantly decreased triglyceride (p < .001), total cholesterol (p < .001), low-density lipoprotein (p < .001), fasting blood sugar (p < .001), and diastolic blood pressure (p = .003). Some limitations, including notable heterogeneity, low quality of studies, and lack of diversity among research participants, should be considered when interpreting our results. Our outcomes suggest that GS supplementation may improve cardiovascular risk factors. Future large-high-quality RCTs with longer duration and various populations are needed to firmly establish the clinical efficacy of the plant.

Potential use of bio functionalized nanoparticles to attenuate triple negative breast cancer (MDA-MB-231 cells).

This study showed that bio-functional silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs) were synthesized in aqueous extracts of Gymnema sylvestre leaves and tested for toxicity assessment against triple-negative breast cancer cells (TNBC). Biofunctional nanoparticle (NPs) samples were characterized using UV-Vis spectroscopy, FT-IR, XRD, SEM, and TEM. The results showed that the phytofabrication of AgNPs resulted in a dark brown, UV-vis maximum absorbance peak at 413 nm. The AgNPs were crystalline and spherical, with sizes ranging from 20 to 60 nm, as confirmed by the XRD pattern and TEM images. Another phytofabrication of ZnONPs exhibited a white precipitate corresponding to a UV-Vis maximum absorption peak at 377 nm and a fine micro flower morphology with a particle-sized tribution between 100 and 200 nm. In addition, FT-IR spectra showed that bioorganic compounds are associated with NPs that respond to reduced Ag+ ions and AgNPs tabilizers. Invitro cytotoxicity studies revealed the potent anti-cancer effects of phytofabricated AgNPs and ZnONPs on TNBC cells. Furthermore, the AO/EB double staining assay results proved that apoptotic cells are distinguished by greenish-yellow fluorescence of the cell nuclei with IC50 concentrations of 44 ± 0.8 µg/mL for AgNPs and 26.2 ± 0.5 µg/mL for ZnONPs, respectively. Based on our results, we expect that the anticancer function of the biofunctional NPs is due to the apoptotic activation of TNBC cells by increased ROS. Therefore, the presented study demonstrated that biofunctional AgNPs and ZnONPs have excellent prospects for the anti-cancer activity that can be used in pharmaceutical and medical fields.

Anti-inflammatory and antioxidant activities of Gymnema Sylvestre extract rescue acute respiratory distress syndrome in rats via modulating the NF-κB/MAPK pathway.

Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality in COVID-19 patients, due to limited therapeutic options. This prompted us to explore natural sources to mitigate this condition. Gymnema Sylvestre (GS) is an ancient medicinal plant known to have various therapeutic effects. This investigation examined the therapeutic effect of hydroalcoholic extract of Gymnema Sylvestre (HAEGS) against lipopolysaccharide (LPS)-induced lung injury and ARDS in in vitro and in vivo models. UHPLC-HRMS/GC-MS was employed for characterizing the HAEGS and identified several active derivatives including gymnemic acid, gymnemasaponins, gymnemoside, gymnemasin, quercetin, and long fatty acids. Gene expression by RT-qPCR and DCFDA analysis by flow cytometry revealed that several inflammatory cytokine/chemokine, cell injury markers, and reactive oxygen species (ROS) levels were highly upregulated in LPS control and were significantly reduced upon HAEGS treatment. Consistent with the in vitro studies, we found that in LPS-induced ARDS model, pre-treatment with HAEGS significantly suppressed the LPS-induced elevation of inflammatory cell infiltrations, cytokine/chemokine marker expression, ROS levels, and lung injury in a dose-dependent manner. Further mechanistic studies demonstrated that HAEGS suppressed oxidative stress by modulating the NRF2 pathway and ameliorated the ARDS through the NF-κB/MAPK signalling pathway. Additional fractionation results revealed that fraction 6 which has the exclusive composition of gymnemic acid derivatives showed better anti-inflammatory effects (inhibition of IL-6 and IL-1ß) at lower concentrations compared to HAEGS. Overall, HAEGS significantly mitigated LPS-induced lung injury and ARDS by targeting the NF-κB/MAPK signalling pathway. Thus, our work unravels the protective role of HAEGS for the first time in managing ARDS.

Optimisation and evaluation of Gymnema sylvestre extract loaded polymeric nanoparticles for enhancement of in vivo efficacy and reduction of toxicity.

AIM: This work studies the development and evaluation of Gymnema sylvestre (GYM) extract loaded sustained release polymeric nanoparticles (PNPs) for enhanced bioavailability and reduced nephrotoxicity. The current therapy is associated with the drawbacks of addiction and repeated administration. METHOD: The sustained release PNPs were developed and evaluated for toxicity. PNPs of GYM were prepared by double emulsion solvent evaporation technique utilising Taguchi model and evaluated for physicochemical properties (particle size, zeta potential, entrapment efficiency), in vitro drug release, compatibility, and stability. Further, the bioavailability and in vivo nephrotoxicity studies in diabetic rat model were also carried out. RESULT: The developed optimised nanoparticles were 205.7 ± 1.20 nm in size, -40.68 mV zeta potential, compatible, and stable in nature with improved entrapment efficiency (67.1 ± 0.2%) and sustained release. Moreover, nanoparticles were found to lower the blood glucose level in single as well as multiple doses. Results of in vivo study indicated that GYM-NPs increased the phosphorylase activity and thus enhanced insulin secretion. Furthermore, the nanoparticles were free from toxicity, which was confirmed by the estimation of kidney biomarker. CONCLUSION: The nanoparticles increased the bioavailability of GYM extract and have a great potential for the treatment of diabetes in reduced dose, and so these can be potential candidates for treating diabetes.

Protective and therapeutic effects of natural products against diabetes mellitus via regenerating pancreatic ß-cells and restoring their dysfunction.

Diabetes mellitus is a growing public health concern and an increasing interest has been raised to search for new compounds with therapeutic effects on ß-cells. There are chronic insulin resistance and loss of ß-cell mass in the case of type-2 diabetes which covers about 90% of total diabetic patients. This work aims to critically review the protective and regenerative effects of various antidiabetic natural products on pancreatic ß-cells. A thorough literature survey was conducted on the natural molecules and extracts having a protective, regenerative, and repairing effect on ß-cells. The primary source of the literature was online scientific databases such as PubMed, Scopus, and Google Scholar. Besides, selected relevant textbooks were also consulted. Various natural molecules including berberine, curcumin, mangiferin, stevioside and capsaicin, and extracts obtained from the plants like Capsicum annum, Gymnema sylvestre, Stevia rebaudiana and Nymphaea stellate, were found to produce regenerative and anti-apoptosis effects on ß-cells. These natural products were also found to increase insulin secretion by stimulating ß-cells. The present review concluded that a large number of molecules and extracts, abundantly found in nature, possess antidiabetic effect via targeting ß-cells. Further research is warranted to use these agents as a drug against diabetes.

The effect of Gymnema sylvestre supplementation on glycemic control in type 2 diabetes patients: A systematic review and meta-analysis.

This systematic review and meta-analysis aims to find the effect of Gymnema sylvestre (GS) supplementation on glycemic control in type-2 diabetes mellitus (T2DM). PubMed, Cochrane library, Google Scholar, and Science Direct were searched from inception to June 2020 to identify the studies that reported GS supplementation on glycemic parameters. Standardized mean difference (SMD) was calculated by comparing the post-intervention data with baseline data. SMDs with 95% confidence intervals (CIs) were pooled using a random-effects model. Our meta-analysis consisting of 10 studies with a total of 419 participants showed that GS supplementation significantly reduces fasting blood glucose (FBG) (SMD 1.57 mg/dl, 95% CI 2.22 to -0.93, p < .0001, I2 90%), postprandial blood glucose (PPBG) (SMD 1.04 mg/dl, 95% CI 1.53 to -0.54, p < .0001, I2 80%), and glycated haemoglobin (HbA1c) (SMD 3.91, 95% CI 7.35 to -0.16%, p < .0001, I2 99%) compared to baseline. Further, our study also found that GS significantly reduces triglycerides (SMD 1.81 mg/dl, 95% CI 2.95 to -0.66, p < .0001, I2 : 96%), and total cholesterol (SMD 4.10 mg/dl, 95% CI 7.21 to -0.99, p < .0001, I2 : 98%) compared to baseline. Our study shows that GS supplementation is effective in improving glycemic control and reducing lipid levels in T2DM patients and suggests that such supplementation might be used as an effective therapy for the management of T2DM and its associated complications to an extent.

Identification of C21 Steroidal Glycosides from Gymnema sylvestre (Retz.) and Evaluation of Their Glucose Uptake Activities.

Gymnema sylvestre (Retz.) Schult is a multi-purpose traditional medicine that has long been used for the treatment of various diseases. To discover the potential bioactive composition of G. sylvestre, a chemical investigation was thus performed. In this research, four new C21 steroidal glycosides sylvepregosides A-D (1-4) were isolated along with four known compounds, gymnepregoside H (5), deacetylkidjoladinin (6), gymnepregoside G (7) and gymnepregoside I (8), from the ethyl acetate fraction of G. sylvestre. The structures of the new compounds were established by extensive 1D and 2D nuclear magnetic resonance (NMR) spectra with mass spectroscopy data. Compounds 1-6 promoted glucose uptake by the range of 1.10- to 2.37-fold, respectively. Compound 1 showed the most potent glucose uptake, with 1.37-fold enhancement. Further study showed that compounds 1 and 5 could promote GLUT-4 fusion with the plasma membrane in L6 cells. The result attained in this study indicated that the separation and characterization of these compounds play an important role in the research and development of new anti-diabetic drugs and pharmaceutical industry.