Steroidal Sapogenins Research Articles

Diosgenin-Loaded Silver Nanoparticles Mitigate B[a]P-Induced Lung Fibrosis Through Modulation of Oxidative Stress and Inflammatory Pathways.

Lung fibrosis, characterized by the thickening and scarring of lung tissue, is a serious condition often triggered by environmental toxins like Benzo[a]pyrene (B[a]P). Diosgenin, a natural steroidal sapogenin found in plants such as fenugreek and wild yam, has shown potential to protect against lung damage due to its anti-inflammatory and antioxidant properties. However, its clinical application is limited by poor solubility and bioavailability. The current investigation aims at developing diosgenin-loaded silver nanoparticles (DioAgNPs) to enhance their delivery and efficacy. This study investigates the preparation, characterization, and protective effects of Dio-AgNPs against B[a]P-induced lung fibrosis in mice. Acute toxicity studies in mice were conducted to determine the lethal dose (LD50) of DioAgNPs. Sub-lethal doses (1/50 and 1/20 LD50) were selected for subsequent experiments. Mice were exposed to B[a]P to induce lung fibrosis. Dio-AgNPs were administered to assess their protective effects. Biochemical assays measured levels of total cholesterol (TC), triglycerides (TG), malondialdehyde (MDA), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-12 (MMP12). Additionally, high-density lipoprotein cholesterol (HDL-C), glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx) levels were evaluated. Quantitative PCR (qPCR) was used to analyze the expression levels of lung signal transducer and activator of transcription 3 (STAT3), transforming growth factor- β1(TGF-β1), and Sirtuin 1 genes. Insilico molecular docking studies were performed to evaluate the binding affinity of diosgenin with SIRT1, STAT3, and TGF-β1 proteins, with binding energies (ΔG) calculated to predict interaction strength. The synthesized Dio-AgNPs exhibited a mean diameter of 51.60±1.54 nm, a zeta potential of -19.5 mV, and encapsulation efficiency of 84.98%, confirming their stability through spectral analysis. In B[a]P-exposed mice, there was a significant elevation in TC, TG, MDA, NF-κB, IL-6, MMP2, and MMP12 levels, alongside a reduction in HDL-C, GSH, CAT, and glutathione peroxidase (GPx) levels. Additionally, lung STAT3 and TGF-β1 gene expression was upregulated, while SIRT1 gene expression was downregulated. Administration of Dio-AgNPs to B[a]P-treated mice resulted in a significant reduction in TC, TG, and HDL-C levels, improvement in lung MDA, NF-κB, IL-6, MMP2, and MMP12 levels, downregulation of lung STAT3 and TGF-β1, and upregulation of SIRT1 gene expression. In-silico molecular docking studies demonstrated strong binding affinities of diosgenin with SIRT1, STAT3, and TGF-β1 proteins, with binding energies (ΔG) of -9.7, -9.6, - 10.1, and -9.7 kcal/mol, respectively. This study innovatively enhances the delivery and efficacy of diosgenin by developing diosgenin-loaded silver nanoparticles (Dio-AgNPs), addressing its solubility and bioavailability challenges. Dio-AgNPs demonstrated significant protective effects against B[a]P-induced lung fibrosis in mice, reducing oxidative stress and inflammation while modulating key genes like STAT3, TGF-β1, and SIRT1. Molecular docking studies confirmed strong binding affinities, underscoring the therapeutic potential of Dio-AgNPs. This research marks a significant advancement in nanomedicine and respiratory therapy, offering a promising approach to managing lung fibrosis and related conditions.

From Plant to Pathway: Molecular Mechanisms of Ruscogenin in Preventing Amyloid-Beta Aggregation through Computational and Experimental Approaches.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, extracellular amyloid-β (Aβ) plaque accumulation, and intracellular neurofibrillary tangles. Recent efforts to find effective therapies have increased interest in natural compounds with multifaceted effects on AD pathology. This study explores natural compounds for their potential to mitigate AD pathology using molecular docking, ADME screening, and in vitro assays, with ruscogenin─a steroidal sapogenin from Ruscus aculeatus─emerging as a promising candidate. Ruscogenin, known for its antioxidant and anti-inflammatory properties, was investigated for its effects on Aβ aggregation, a critical process in AD progression. In vitro assays demonstrated that ruscogenin inhibits Aβ oligomerization at equimolar and higher molar ratios. Molecular dynamics (MD) simulations further revealed that ruscogenin targets aggregation-prone regions, reducing noncovalent interactions and the solvent-accessible surface area of Aβ aggregates. These effects were concentration-dependent, with higher concentrations yielding optimal inhibition, pointing to a multiphasic behavior in ruscogenin's modulation of Aβ aggregation. This study highlights ruscogenin's potential as a natural therapeutic agent for AD, capable of addressing both oxidative stress and inflammation. The findings lay the groundwork for further exploration of ruscogenin-based interventions and underscore the broader potential of natural compounds in AD treatment strategies.

Diosgenin Unveiled: From Nutritional Insights to Nano Applications and Molecular Marvels

Introduction: Diosgenin (DSG) is a steroidal sapogenin found in plants such as Dioscorea tokoro Makino ex Miyabe, Trigonella foenum-graceum, and Solanum virgini-anum, and is utilized as a natural source of steroidal hormones. It exhibits anti-inflammatory, anti-apoptotic, anti-oxidant, and various other pharmacological properties, making it a relia-ble candidate for research purposes. The aim of this review is to provide researchers with a scientific basis for the target-specific bio-potential of DSG as an ethnomedicine and to under-score its potential for drug design and therapy modifications in the future. Methods: Relevant literature search up to the current year by using online databases such as Scopus, Google Scholar, PubMed, Research Gate, and Science Direct by applying related search terms. Results: This review first addressed the green nanotechnology that is widely adopted to improve DSG’s pharmacokinetic profile, and then listed numerous nano-formulations of DSG for enhancement of their physical properties. At last, this article ex-plored the molecular action of DSG on NF-ĸB, TGF-β1/Smad, AMPK/ACC/CPT-1A & SERBP-1c/FAS, etc. that are pathologically involved in a variety of diseases for better under-standing such as limited clinical research has been conducted to date. Conclusion: Overall, the current review tries to update all information about DSG's nutri-tional benefits, its application as nanomedicine, and diverse pharmacological actions based on various molecular targets for its commendable pre-clinical and clinical applications

Ultrasound-assisted Co-extraction and characterization of saponin-rich Co-extracts from fenugreek seeds (Trigonella foenum-graecum L.) and quinoa husk (Chenopodium quinoa Willd.) and their hydrolysates

The co-extraction of steroidal and triterpenoid saponins, followed by hydrolysis to produce sapogenin-rich extracts, offers an efficient strategy to enhance the multi-bioactive potential of extracts. The resulting chemical composition modifications, including the presence of other co-extracted or co-hydrolyzed compounds, must also be considered. In this study, ultrasound-assisted co-extraction of fenugreek seeds and quinoa husk using methanol and 50% aqueous methanol was conducted to obtain extracts and co-extracts with varying proportions of steroidal and triterpenoid saponins, in ratios of 0:100, 25:75, 50:50, 75:25, and 100:0, respectively. Aqueous methanol produced the highest extraction yields (15–25%) and saponin contents (40–70%) in the extracts and co-extracts. The conversion by microwave-assisted acid hydrolysis of saponins to sapogenins was more efficient for triterpenoid saponins, leading to a higher triterpenoid sapogenin content in all co-extracts, accounting for over 70% of the total sapogenins. The co-extracts also contained other bioactive compounds, such as phenolic compounds (3–4 g/100 g), with their content being favored by the presence of fenugreek. Hydrolysis altered the overall composition of the saponin-rich co-extracts, enriching the resulting hydrolyzed products in both types of sapogenins, along with fatty acids, carbonyls, non-protein nitrogen compounds and organic acids, while reducing monoglycerides, removing carbohydrates and significantly modifying the phenolic profile by eliminating many original phenolic compounds and generating new ones. Therefore, co-extraction and post-extraction hydrolysis of fenugreek and quinoa allowed the combination of triterpenoid and steroidal saponins or sapogenins into single products, along with other specific compounds from both sources.

Diosgenin upregulates axonal guidance partner molecules, Galectin-1 and Secernin-1

Galectin-1, a β-galactosides-binding protein, is widely expressed in various tissues and exhibits diverse biological activities. We previously obtained following findings; 1) Diosgenin, a steroid sapogenin, promoted axonal regeneration in the brain and recovered memory deficits in a model of Alzheimer’s disease (AD), 5XFAD mouse; 2) Neuron-specific overexpression of Galectin-1 protein in the hippocampus recovered memory impairment and promoted axonal regeneration in the brain in 5XFAD mice; 3) Secernin-1, a counterpart and axonal guidance molecule for Galectin-1-expressing axons, was secreted from the prefrontal cortical neurons to promote axonal guidance from the hippocampus to the prefrontal cortex. However, it has never been elucidated that diosgenin signaling increase Galectin-1 and Secernin-1 or not. Here, we found that diosgenin treatment upregulated the protein level of Galectin-1 in the hippocampus both in primary cultured neurons and in 5XFAD mouse brains. In addition, diosgenin-induced upregulation of Galectin-1 was diminished by treatment of a neutralizing antibody of 1,25D3-membrane-associated rapid response steroid-binding receptor (1,25D3-MARRS), a direct binding receptor for diosgenin. Importantly, knockdown of Galectin-1 in hippocampal neurons inhibited axonal growth activity of diosgenin. Furthermore, the expression level of Secernin-1 was also increased in prefrontal cortical neurons by administration of diosgenin to 5XFAD mice. These findings suggest that diosgenin is a suitable compound to facilitate Galectin-1-Secernin-1-mediated axonal growth in AD brains.

Elicitor-enhanced steroidal sapogenin accumulation in hairy root cultures of Trigonella foenum-graecum

In current work, we studied hairy root induction in Trigonella foenum graecum, which is an important medicinal plant, and examined the impact of different elicitors on some phytochemical characteristics and metabolites production in hairy root cultures. Accordingly, some factors such as five strain types of Agrobacterium rhizogenes (1724, 15834, A4, A13 and MSU) and three different explants, namely leaf, cotyledon and hypocotyl were studied. The results showed that different A. rhizogenes strains exhibited different infection efficiency. MSU and 15834 had highest efficiency of hairy root induction than other strains. Also, hairy root induction frequency in leaf explants was higher than in other explants. Salicylic acid (SA), nitric oxide (NO), CaCl2 and penconazole (PEN) were used in elicitation process. Hairy roots were treated with SA (0.1 and 0.5 mM), NO (10 and 50 µM), CaCl2 (5 and 10 mM) and PEN (5 and 10 mg/L). Applied elicitors enhanced antioxidant enzymes activities and reduced oxidative stress markers; this observation might be ascribed to regulation of the oxidative status of the elicited cells. Significant increase of antioxidant metabolites (total phenol, flavonoid and anthocyanin) in PEN-treated hairy roots was associated to phenylalanine ammonia lyase activity, indicating an up-regulation of phenylpropanoid/flavonoid metabolism. PEN and CaCl2 treatment enhanced steroidal sapogenin in hairy root cultures. These results suggested that use of elicitors can enhance the production of secondary metabolites in transformed hairy roots. Among the elicitors applied, CaCl2 and PEN were the most effective in increasing secondary metabolite production in transformed hairy roots of T. foenum graecum.

The Protective Effects of Ruscogenin Against Lipopolysaccharide-Induced Myocardial Injury in Septic Mice.

Sepsis-induced myocardial dysfunction commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. This study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. In addition, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NOD-like receptor protein-3 (NLRP3) upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for sepsis-induced myocardial dysfunction therapy.

Ruscogenin Attenuates Ulcerative Colitis in Mice by Inhibiting Caspase-1-Dependent Pyroptosis via the TLR4/NF-κB Signaling Pathway.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders affecting the digestive tract, including ulcerative colitis and Crohn's disease. Ruscogenin, a prominent steroidal sapogenin present in radix ophiopogon japonicus, has shown a protective effect on attenuating the inflammatory response associated with inflammatory diseases, but the efficacy of ruscogenin in IBD remains unclear. The aim of this study is to explore the effect of ruscogenin on intestinal barrier dysfunction and inflammatory responses as well as the underlying mechanism in ulcerative colitis. A dextran sulfate sodium salt (DSS)-induced C57BL/6 mouse colitis model was employed for the in vivo studies, while in vitro experiments were performed in THP-1 cells and human intestinal epithelial cells involved in inducing inflammatory responses and pyroptosis using LPS/nigericin. The results indicated that ruscogenin treatment attenuated the symptoms of ulcerative colitis, reduced the release of inflammatory cytokines and the expression of pyroptosis-associated proteins, and restored the integrity of the intestinal epithelial barrier in colon tissue in mice. Moreover, ruscogenin inhibited LPS/nigericin-induced pyroptosis in THP-1 cells. Mechanically, ruscogenin inhibited NLRP3 inflammasome activation and canonical pyroptosis, at least in part, through the suppression of the TLR4/NF-κB signaling pathway. These findings might provide new insights and a solid foundation for further exploration into the therapeutic potential of ruscogenin in the treatment of IBD.

Diosgenin inhibits proliferation and migration of ovarian cancer cells and induce apoptosis via upregulation of PTEN.

Diosgenin, a natural steroidal sapogenin, has recently attracted a high amount of attention, as an effective anticancer agent in ovarian cancer. However, diosgenin mediated anticancer impacts are still not completely understood. Thus, the present study evaluated the effect of diosgenin on the proliferation, apoptosis, and metastasis of ovarian cancer cells. OVCAR-3 and SKOV-3 cells were treated with diosgenin, cellular viability was assessed by MTT assay and apoptosis was measured by ELISA and evaluated the protein expression levels of apoptotic markers through western blotting. Cell migration was examined by measuring the mRNA levels of genes involved in the cell invasion. The protein expression levels of main components of PI3K signaling were evaluated via western blotting. Diosgenin led to significant inhibition of cellular proliferation in a dose-dependent manner. It also induced apoptosis through upregulating pro-apoptotic markers and downregulating antiapoptotic mediators. In addition, OVCAR-3 cells exposure to diosgenin decreased cell migration and invasion. More importantly, diosgenin downregulated the expression levels of main proteins in PI3K signaling including PI3K, Akt, mTOR, and GSK3. Diosgenin inhibited the proliferation and migration of OVCAR-3 ovarian cancer cells and induced apoptosis, which may be mediated by targeting PI3K signaling.

In vitro evaluation of the susceptibility of bacterial biofilms to hecogenin acetate

Biofilms are a bacterial resistance strategy through which microorganisms organize themselves in the form of a colony fixed to a surface that is protected by a polymer matrix. Infectious diseases that result in biofilm formation have been considered a relevant public health problem due to the potential to increase patient morbidity and mortality, in addition to increasing the burden on health services. Such pathologies are treated with the use of antimicrobial drugs, the indiscriminate use of which has contributed to the process of bacterial resistance, demanding the need to invest in new alternatives to combat them. Based on this, the present work aimed to evaluate the anti-biofilm formation and eradication capacity of Hecogenin Acetate, a steroidal sapogenin of natural origin with important antibacterial properties. For this, we used strains of Streptococcus mutans INCQS 00,446 (ATCC 25,175), Enterococcus faecalis INCQS 00,018 (ATCC 14,506), Staphylococcus epidermidis INCQS 00,016 (ATCC 12,228), Staphylococcus aureus ATCC 25,923, Pseudomonas aeruginosa ATCC 9027 and Escherichia coli ATCC 259,223. The formation, formation inhibition and treatment assays were carried out in microdilution plates and revealed using the crystal violet method. Readings were carried out using absorbance at wavelengths of 492 nm. All tests were performed in triplicate and statistical analyzes were performed using Graphpad Prism v.5.0 software. It was observed that the bacterial strains used have a relevant capacity for biofilm formation, with the Gram positive ones identified in the present study as the best former. In the results of the analyzes with bacterial biofilm, it was identified that Hecogenin Acetate had a relevant antibiofilm capacity, and could therefore serve as a basis for further research into the development of new antimicrobial drugs.

Preliminary Qualitative Analysis of Plant Samples by High-performance Thin-layer Chromatography for the Presence of Steroid Sapogenins of Some Representatives of the Dioscoreacae, Fabaceae, Ranunculaceae, Melanthiaceae, Scrophulariaceae

Introduction. Results of original research carried out by means of high performance thin layer chromatography (HPTLC) of various plant samples (air-dry raw material) of Dioscoreaceae, Ranunculaceae, Fabaceae, Melanthiaceae, Scrophulariaceae families are presented in this article.Aim. To carry out preliminary qualitative analysis by HPTLC method of steroidal sapogenins composition in hydrolyzed extracts, obtained from vegetative samples of above-ground and underground organs of some Dioscoreaceae, Ranunculaceae, Fabaceae, Melanthiaceae, Scrophulariaceae families.Materials and methods. Extraction from pre-dehydrated raw materials was carried out with 50 % aqueous isopropanol (c.p.) in an ultrasonic bath, followed by acidic hydrolysis of O-glycoside bonds, evaporation and redissolution of dry residue in 99 % methanol (c.p.); purification from suspended solids by filtering through filters with 20 µm perforation diameter. HPTLC was performed on apparatus complex CAMAG (Switzerland) using HPTLC Aluminium sheets Silica gel 60 F254 plates 20 × 20 cm, which were cut to the size 20 × 10 cm.Results and discussion. After scanning densitometry at 254 nm, we found that the separation of isopropanol extracts, followed by redissolution in strong methanol in this solvent system allows a fairly acceptable separation and identification of the compounds studied. Comparison of the tracks of plant extracts was performed with standard samples of steroid sapogenins, whose methanol solutions were applied to one stain-strobe of track 1, provided that they had different Rf indices and coloration after derivatization.Conclusion. Diosgenin was identified in plant extracts of rhizomes and roots of Dioscorea nipponica and Dioscorea caucasica and in seeds of Trigonella foenum-graecum preliminarily. Sarsasapogenin was verified in extracts of fruits of Sophora japonica, tigogenin in extracts of seeds of Trigonella foenum-graecum, herb of Pulsatilla patens and herb of Veronica officinalis. Yamogenin was detected in extracts of seeds of Trigonella foenum-graecum and herb of Veronica officinalis. This work is exploratory in nature, assessing the presence of certain saponins by their sapogenins in selected extracts. We will optimize the HPLC separation procedure and choose other detection methods to unambiguously assess the co-presence of the studied sapogenins with approximately the same staining shades after derivatization and matching retention indices: there are pairs of steroidal sapogenins that have the same retention, we decided to group them in mixtures so that there would be separation within the group and subsequent comparison with the original extracts would make it possible to identify those or other sapogenins in such extracts.

Anticancer Potential of Biologically Active Diosgenin and its Derivatives: An Update

Abstract: Diosgenin (1) is an important steroidal metabolite often used as a precursor material for the synthesis of a broad array of steroidal drugs. Recent studies have indicated that compound (1) and many diosgenyl derivatives such as (1→9) possess both in vivo and in vitro biological activities like antioxidant, hypolipidemic, antithrombotic, immuno-modulatory, and estrogenic including anticancer activities. This steroidal sapogenin is of increasing interest in the pharmaceutical industry as it is being explored as an important starting material for the synthesis of oral contraceptives, sex hormones, and many other steroidal drugs having anticancer potential. Naturally occurring diosgenin, and its glucoside derivatives are quite abundant in several plant sources, but very little is known about the biogenesis of this class of secondary plant metabolites. Hence, designing a semi-synthetic protocol for the improved anticancer potential with enhanced efficacy of diosgenin and its derivatives is always a challenging field of cutting-edge research in pharmaceutical chemistry. The present review highlights some of the recent research findings and applications of this group of triterpenoids as a potential anticancer agent.

Exploring the anti-angiogenic properties of diosgenin saponin from Trigonella graecum (fenugreek): A study on Zebrafish embryos

Background: Angiogenesis plays a role in both physiological and pathological processes such as wound healing, embryonic development, and cancer metastasis, and it is the process by which new blood vessels are formed from existing ones. Diosgenin is a naturally occurring steroidal sapogenin found in plants such as yam and fenugreek, which is a compound of interest because of its pharmacological properties, including anti-carcinogenic effects. Zebrafish embryos are used due to their translucent nature, which facilitates the direct observation of vascular development. Aims and Objectives: The purpose of this study is to utilize zebrafish embryos to examine the impact of diosgenin on angiogenesis. It specifically aims to determine whether diosgenin could inhibit the development of inter-segmental vessels (ISV) in zebrafish embryos and also to investigate its effect on vascular endothelial growth factor (VEGF-A), a key regulator of angiogenesis. Materials and Methods: To explore the anti-angiogenic properties of diosgenin, we performed in vivo experiments using the zebrafish angiogenesis model. This involved staining red blood cells with O-dianisidine and conducting semiquantitative real-time polymerase chain reaction analysis to assess VEGF-A mRNA expression levels. Results: Diosgenin was shown to hinder the growth and formation of ISV in dosage-dependent development using a red blood cell staining assay when compared to the positive control, SU5416. In addition, there was a significant decrease in VEGF-A expression. Conclusion: In the presence of diosgenin, there is an evidence of inhibition of ISV development and suppression of VEGF mRNA expression. These findings underscore the therapeutic potential of diosgenin for targeting angiogenesis in cancer. However, further research is needed to understand the mechanism underlying diosgenin’s effect and its clinical relevance.

The Synthesis of Novel aza-Steroids and α, β-Unsaturated-Cyanoketone from Diosgenin.

Recent studies have demonstrated the antiproliferative and cytotoxic effects of aza-steroids and steroidal sapogenins on human cancer cell lines. The scientific community has shown a growing interest in these compounds as drug candidates for cancer treatment. In the current work, we report the synthesis of new diosgenin oxime derivatives as potential antiproliferative agents. From (25 R)-5α-spirost-3,5,6-triol (1), a diosgenin derivative, ketones 2, 3, 4, and 9 were obtained and used as precursors of the new oximes. A condensation reaction was carried out between the steroidal ketones (2, 3, 4, and 9) with hydroxylamine hydrochloride in 2,4,6-trimethylpyridine to produce five spirostanic oximes (four of them are not reported before) with a 42-96% yield. Also, a new spirostanic α, β-unsaturated cyanoketone was synthesized via Beckmann fragmentation using thionyl chloride with a 62% yield. Furthermore, we proposed a reaction mechanism with the aim of explaining such transformation.

Preparation Of Diosgenin-Encapsulated Microspheres By Spray Drying Technique

Diosgenin, a naturally occurring steroid sapogenin possessing diverse therapeutic properties, represents a bioactive compound of interest. However, its complete pharmaceutical utilization has been impeded by inherent challenges, primarily associated with poor aqueous solubility and stability. In the present investigation, we introduce an innovative methodology for fabricating diosgenin-encapsulated microspheres through the utilization of the spray drying technique. The spray drying process involves the transformation of a solution containing diosgenin into finely dispersed microspheres through atomization, followed by rapid drying in a hot air stream. Various formulation parameters, encompassing the selection of encapsulating material, surfactants, and process conditions, were methodically optimized to attain elevated encapsulation efficiency and precise control over release characteristics. The microspheres thus prepared underwent assessment for percentage yield, encapsulation efficiency, particle size, and in vitro drug release. Results indicate the generation of uniform microspheres exhibiting heightened diosgenin encapsulation and enhanced physical stability. Additionally, in vitro release studies demonstrated sustained and controlled diosgenin release from the microspheres, underscoring their potential for protracted therapeutic effects. Encapsulation efficiency, release kinetics, and physicochemical attributes of the microspheres were found to be contingent upon the choice of encapsulating material and process parameters. In conclusion, the fabrication of diosgenin-encapsulated microspheres employing the spray drying technique represents a promising strategy to augment the bioavailability and therapeutic efficacy of diosgenin. These microspheres hold considerable promise for applications within the pharmaceutical and nutraceuticals industries serving as a platform for the advancement of innovative drug delivery systems.

Diosgenin prevents dexamethasone-induced myotube atrophy in C2C12 cells

Several pathophysiological abnormalities, including a sedentary lifestyle, chronic diseases, and oxidative stress, can contribute to muscle atrophy triggered by an imbalance in muscle protein synthesis and degradation. Resolving muscle atrophy is a critical issue as it can reduce the quality of life. Here, one of the promising functional food factors, diosgenin (a steroidal sapogenin) showed strong preventive activities against dexamethasone (Dex)-induced muscle atrophy, as determined by the expression levels and morphology of the myosin heavy chain in C2C12 myotubes. Diosgenin inhibited protein expressions of Dex-induced skeletal muscle-specific ubiquitin ligase, including muscle RING finger 1 (MuRF1) and casitas B-lineage lymphoma protooncogene b (Cbl-b) but not atrogin-1. Diosgenin ameliorated Dex-induced declines of Akt phosphorylation at Ser473 and FoxO3a phosphorylation at Ser253, which probably at least partially contributed to the suppression of MuRF1, Cbl-b, and atrogin-1 gene expression. Additionally, diosgenin inhibited Dex-induced nuclear translocation of the glucocorticoid receptor (GR), diosgenin therefore may competitively inhibit the interaction between Dex and GR. These findings suggest that diosgenin is an effective functional food for preventing glucocorticoid-induced skeletal muscle atrophy.

Literature review on hepatoprotective effects of diosgenin: possible mechanisms of action.

Liver diseases are among the major causes of death worldwide. Alcohol consumption, obesity, diabetes mellitus, viral infection, and drug-induced liver injury are common risk factors for the development of liver diseases. Diosgenin is a herbal steroidal sapogenin with hepatoprotective properties. This phytosteroid modulates lipid profile and prevents liver injury and fibrosis, metabolic associated fatty liver disease (MAFLD), steatohepatitis, and diabetes mellitus. Different mechanisms have been presented underlying the therapeutic properties of diosgenin. Diosgenin with antioxidant activity and ability to inhibit pro-inflammatory and apoptotic mediators as well as modulating gut microbiota is able to protect the liver. This literature overview summarizes the previously published studies regarding the hepatoprotective function of diosgenin against liver injury in different conditions with an emphasis on possible underlying mechanisms.

Ruscogenin timing administration mitigates cerebral ischemia-reperfusion injury through regulating circadian genes and activating Nrf2 pathway

BackgroundRuscogenin (Rus), a steroidal sapogenin extracted from Ophiopogon japonicus (L. f.) Ker-Gawl., has the effect of alleviating cerebral ischemia-reperfusion injury (IRI), acute lung injury. At present, the chronopharmacological effects of Rus are still unknown. PurposeThis study explored the alleviating effect and mechanism of Rus timing administration on mice cerebral IRI. MethodsThe animals in different groups were administrated Rus (10 mg/kg) by gavage at four time points (23:00–01:00, 05:00–07:00, 11:00–13:00, 17:00–19:00) respectively for 3 days. On the 4th day, middle cerebral artery occlusion (MCAO) surgery was operated during 5:00–7:00. Behavioral tests were executed and the brain was collected for infarct volume, qPCR and immunoblot detection. The levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin-1beta (IL-1β) and inducible nitric oxide synthase (iNOS) were detected by qPCR. Glutathione (GSH), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in serum and cerebral cortex were detected. The clock genes were tested by western blot. Based on these results, 17:00–19:00 was selected to administrate Rus for further mechanism study and Nrf2 blocker group was administrated all-trans-retinoic acid (ATRA) at 14:00 for 3 days. ResultsAdministration of Rus reduced cerebral infarcted volume, ameliorated the behavior score and upregulated the mRNA and protein expression of Per1, Bmal1, Clock, Rev-erbα, transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1). Administration of Rus during 17:00–19:00 had better preventive effect than other three time points. Combined administration of ATRA blunted the preventive effect of Rus. ConclusionThe preventive effect of Rus is affected by the time of administration, which was regulated by Nrf2 pathway. Taken together, we provide solid evidence to suggest that different administration time point affect the effectiveness of Rus in alleviating IRI.

Diosgenin prevents periodontitis by inhibiting inflammation and promoting osteogenic differentiation.

Diosgenin, an essential dietary steroidal sapogenin, possess multiple pharmacological activities. This study aimed to assess the effects of diosgenin on periodontitis and elucidate the mechanisms. Lipopolysaccharide (LPS)-stimulated human periodontal ligament stem cells (hPDLCs) and a Porphyromonas gingivalis (P.g) plus ligation-induced animal model were used for in vitro and in vivo studies, respectively. Inflammatory responses, nuclear factor κ-B (NF-κB) signaling and osteogenesis-related markers were measured both in LPS-stimulated hPDLSCs and in gingival tissue of periodontitis rats. Treatment with diosgenin significantly inhibited the production of tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and interleukin (IL)-6 and the activation of NF-κB pathway in LPS-stimulated hPDLSCs. Further, treatment with diosgenin enhanced the expression of osteoblast-related genes and increased the osteogenic differentiation capacity. Further, activation NF-κB pathway largely abolished the protective effects of diosgenin. Consistent with the in vitro studies, in vivo studies showed that administering diosgenin to periodontitis rats significantly lowered the levels of the TNF-α, IL-1β, and IL-6 and the inflammatory transcription factor NF-κB in gingival tissue. In addition, osteoblast-related genes were promoted. Diosgenin attenuates periodontitis by adjusting NF-κB signaling to inhibit inflammatory effects and promoting osteogenesis, suggesting diosgenin might be developed as a therapeutic strategy for treating periodontitis in the future.

Diosgenin normalization of disrupted behavioral and central neurochemical activity after single prolonged stress.

Introduction: Post-traumatic stress disorder (PTSD) is a chronic mental illness triggered by traumatic experiences such as wars, natural disasters, or catastrophes, and it is characterized by anxiety, depression and cognitive impairment. Diosgenin is a steroidal sapogenin with known neuroprotective and antioxidant properties. This study aimed to assess the pharmacological potential of diosgenin in a single prolonged stress (SPS) model of PTSD, plus other behavioral models along with any consequent alterations in brain neurochemistry in male mice. Methodology: SPS was induced by restraining animals for 2h, followed by 20min of forced swim, recuperation for 15min, and finally, exposure to ether to induce anesthesia. The SPS-exposed animals were treated with diosgenin (20, 40, and 60mg/kg) and compared with the positive controls, fluoxetine or donepezil, then they were observed for any changes in anxiety/depression-like behaviors, and cognitive impairment. After behavioral screening, postmortem serotonin, noradrenaline, dopamine, vitamin C, adenosine and its metabolites inosine and hypoxanthine were quantified in the frontal cortex, hippocampus, and striatum by high-performance liquid chromatography. Additionally, animal serum was screened for changes in corticosterone levels. Results: The results showed that diosgenin reversed anxiety- and depression-like behaviors, and ameliorated cognitive impairment in a dose-dependent manner. Additionally, diosgenin restored monoamine and vitamin C levels dose-dependently and modulated adenosine and its metabolites in the brain regions. Diosgenin also reinstated otherwise increased serum corticosterone levels in SPS mice. Conclusion: The findings suggest that diosgenin may be a potential candidate for improving symptoms of PTSD.