Diosgenin loaded cellulose nanoonion impedes different stages of protein aggregation induced cell death via alleviating mitochondrial dysfunction and upregulation of autophagy.

Protein aggregation is a multifaceted phenomenon prevalent in the progression of neurodegenerative diseases, yielding aggregates of diverse sizes. Recently, increased attention has been directed towards early protein aggregates due to their pronounced toxicity, largely stemming from inflammation mediated by reactive oxygen species (ROS). This study advocates for a therapeutic approach focusing on inflammation control rather than mere ROS inhibition in the context of neurodegenerative disorders. Here, we introduced Camellia sinensis cellulose nanoonion (CS-CNO) as an innovative, biocompatible nanocarrier for encapsulating the phytosteroid diosgenin (DGN@CS-CNO). The resulting nano-assembly, manifesting as spherical entities with dimensions averaging ~180-220 nm, exhibits a remarkable capacity for the gradual and sustained release of approximately 39-44 % of DGN over a 60-hour time frame. DGN@CS-CNO displays a striking ability to inhibit or disassemble various phases of hen egg white lysozyme (HEWL) protein aggregates, including the early (HEWLEA) and late (HEWLLA) stages. In vitro experiments employing HEK293 cells underscore the potential of DGN@CS-CNO in mitigating cell death provoked by protein aggregation. This effect is achieved by ameliorating ROS-mediated inflammation and countering mitochondrial dysfunction, as evidenced by alterations in TNFα, TLR4, and MT-CO1 protein expression. Western blot analyses reveal that the gradual and sustained release of DGN from DGN@CS-CNO induces autophagy, a pivotal process in dismantling intracellular amyloid deposits. In summary, this study not only illuminates a path forward but also presents a compelling case for the utilization of phytosteroid as a formidable strategy against neuroinflammation incited by protein aggregation.

Stabilization of all-natural water-in-oil high internal phase pickering emulsion by using diosgenin/soybean phosphatidylethanolamine complex: Characterization and application in 3D printing.

This study aimed to prepare an all-natural water-in-oil high internal phase Pickering emulsion (W/O-HIPPE) using diosgenin/soybean phosphatidylethanolamine complex (DGSP) and investigate the 3D printing performance. Results suggested that the self-assembly of diosgenin crystal was modified by SP in DGSP (diosgenin-SP ratios at 3:1 and 1:1), revealing a variation from large-size outward radiating needle-like to small-size granular-like shape, which facilitated closely packing at the interface. Hydrophilicity of DGSP was also increased (contact angle varying from 133.3 o to 106.4 o), ensuring more adequate interfacial adsorption to reduce interfacial tension more largely (6.5 mN/m). Thus, the W/O-HIPPE made by DGSP with diosgenin-SP = 1:1, exhibited smaller droplets and better freeze/thawing stability. The W/O-HIPPE was also measured improved rheological properties for 3D printing: satisfied shear-thinning behavior, higher recovery and self-supporting (viscoelasticity and deformation resistance). Consequently, the W/O-HIPPE allowed for printing more delicate patterns. This work provided guidance to prepare W/O-HIPPE for 3D printing.

Diosgenyl glucosamine conjugates increase pro-apoptotic and selective activities in cancer cell lines.

BACKGROUND INFORMATION: Antiproliferative and apoptotic activities have been attributed to the phytosteroid diosgenin ((25R)-spirost-5-en-3ß-ol; 1). It is known that combining glucose with two rhamnoses (the chacotrioside framework) linked to diosgenin increases its apoptotic activity. However, the effects of diosgenin glucosamine glycosides on different cancer cell types and cell death have not been entirely explored. RESULTS: This study reports the antiproliferative, cytotoxic, and apoptotic activities of diosgenin and its glycosylated derivative ((25R)-spirost-5-en-3ß-yl ß-D-glucopyranoside; 2). It also explores the effects of two diosgenin glucosamine derivates, diosgenin 2-acetamido-2-deoxy-ß-D-glucopyranoside (3), and diosgenin 2-amino-2-deoxy-ß-D-glucopyranoside hydrochloride (4), on different cancer cell lines. We found that all the compounds affected proliferative activity with minimal toxicity. In addition, all cancer cell lines showed morphological and biochemical characteristics corresponding to an apoptotic process. Apoptotic cell death was higher in all cell lines treated with compounds 2, 3 and 4 than in those treated with diosgenin. Moreover, compounds 3 and 4 induced apoptosis better than compounds 1 and 2. These results suggest that combining glucosamine with modified glucosamine attached to diosgenin has a greater apoptotic effect than diosgenin or its glycosylated derivative (compound 2). Furthermore, diosgenin and the abovementioned glycosides had a selective effect on tumour cells since the proliferative capacity of human lymphocytes, keratinocytes (HaCaT) and epithelial cells (CCD841) was not significantly affected. CONCLUSIONS: Altogether, these results demonstrate that diosgenin glucosamine compounds exert an antiproliferative effect on cancer cell lines and induce apoptotic effects more efficiently than diosgenin alone without affecting non-tumour cells. SIGNIFICANCE: This study evidences the pro-apoptotic and selective activities of diosgenyl glucosamine compounds in cancer cell lines.

Fabrication and evaluation of anticancer potential of diosgenin incorporated chitosan-silver nanoparticles; in vitro, in silico and in vivo studies.

The discovery of effective therapeutic approaches with minimum side effects and their tendency to completely eradicate the disease is the main challenge in the history of cancer treatment. Fenugreek (FGK) seeds are a rich source of phytochemicals, especially Diosgenin (DGN), which shows outstanding anticancer activities. In the present study, chitosan-silver nanoparticles (ChAgNPs) containing Diosgenin (DGN-ChAgNPs) were synthesized and evaluated for their anticancer activity against breast cancer cell line (MCF-7). For the physical characterization, the hydrodynamic diameter and zeta potential of DGN-ChAgNPs were determined to be 160.4 ± 12 nm and +37.19 ± 5.02 mV, respectively. Transmission electron microscopy (TEM) showed that nanoparticles shape was mostly round with smooth edges. Moreover, DGN was efficiently entrapped in nanoformulation with good entrapment efficacy (EE) of ~88 ± 4 %. The in vitro anti-proliferative activity of DGN-ChAgNPs was performed by sulforhodamine B (SRB) assay with promising inhibitory concentration of 6.902 ± 2.79 µg/mL. DAPI staining, comet assay and flow cytometry were performed to validate the anticancer potential of DGN-ChAgNPs both qualitatively and quantitatively. The percentage of survival rate and tumor reduction weight was evaluated in vivo in different groups of mice. Cisplatin was used as a standard anticancer drug. The DGN-ChAgNPs (12.5 mg/kg) treated group revealed higher percentage of survival rate and tumor reduction weight as compared to pure DGN treated group. These findings suggest that DGN-ChAgNPs could be developed as potential treatment therapy for breast cancer.

The Isolation, Identification and Immobilization Method of Three Novel Enzymes with Diosgenin-Producing Activity Derived from an Aspergillus flavus.

Diosgenin is an important raw material used in the synthesis of steroid drugs, and it is widely used in the pharmaceutical industry. The traditional method of producing diosgenin is through using raw materials provided via the plant Dioscorea zingiberensis C. H. Wright (DZW), which is subsequently industrially hydrolyzed using a high quantity of hydrochloric and sulfuric acids at temperatures ranging from 70 °C to 175 °C. This process results in a significant amount of unmanageable wastewater, creates issues of severe environmental pollution and consumes high quantities of energy. As an alternative, the enzymolysis of DZW to produce diosgenin is an environmentally and friendly method with wide-ranging prospects for its application. However, there are still only a few enzymes that are suitable for production on an industrial scale. In this study, three new key enzymes, E1, E2, and E3, with a high conversion stability of diosgenin, were isolated and identified using an enzyme-linked-substrate autography strategy. HPLC-MS/MS identification showed that E1, a 134.45 kDa protein with 1019 amino acids (AAs), is a zinc-dependent protein similar to the M16 family. E2, a 97.89 kDa protein with 910 AAs, is a type of endo-ß-1,3-glucanase. E3, a 51.6 kDa protein with 476 AAs, is a type of Xaa-Pro aminopeptidase. In addition, the method to immobilize these proteins was optimized, and stability was achieved. The results show that the optimal immobilization parameters are 3.5% sodium alginate, 3.45% calcium chloride concentration, 1.4 h fixed time, and pH 8.8; and the recovery rate of enzyme activity can reach 43.98%. A level of 70.3% relative enzyme activity can be obtained after employing six cycles of the optimized technology. Compared with free enzymes, immobilized enzymes have improved stability, acid and alkaline resistance and reusability, which are conducive to large-scale industrial production.

The Functional Characterization of DzCYP72A12-4 Related to Diosgenin Biosynthesis and Drought Adaptability in Dioscorea zingiberensis.

Dioscorea zingiberensis is a perennial herb famous for the production of diosgenin, which is a valuable initial material for the industrial synthesis of steroid drugs. Sterol C26-hydroxylases, such as TfCYP72A616 and PpCYP72A613, play an important role in the diosgenin biosynthesis pathway. In the present study, a novel gene, DzCYP72A12-4, was identified as C26-hydroxylase and was found to be involved in diosgenin biosynthesis, for the first time in D. zingiberensis, using comprehensive methods. Then, the diosgenin heterogenous biosynthesis pathway starting from cholesterol was created in stable transgenic tobacco (Nicotiana tabacum L.) harboring DzCYP90B71(QPZ88854), DzCYP90G6(QPZ88855) and DzCYP72A12-4. Meanwhile, diosgenin was detected in the transgenic tobacco using an ultra-performance liquid chromatography system (Vanquish UPLC 689, Thermo Fisher Scientific, Bremen, Germany) tandem MS (Q Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer, Thermo Fisher Scientific, Bremen, Germany). Further RT-qPCR analysis showed that DzCYP72A12-4 was highly expressed in both rhizomes and leaves and was upregulated under 15% polyethylene glycol (PEG) treatment, indicating that DzCYP72A12-4 may be related to drought resistance. In addition, the germination rate of the diosgenin-producing tobacco seeds was higher than that of the negative controls under 15% PEG pressure. In addition, the concentration of malonaldehyde (MDA) was lower in the diosgenin-producing tobacco seedlings than those of the control, indicating higher drought adaptability. The results of this study provide valuable information for further research on diosgenin biosynthesis in D. zingiberensis and its functions related to drought adaptability.

Epoxide of diosgenin acetate synthesis: DoE for diastereoselective yield optimization, antimicroibial, antioxidant and antiproliferative effects.

Diosgenin and its derivatives have proved a huge importance in diverse biological activities. The optimized production of the diastereoisomers of the epoxide of diosgenin acetate by means of mCPBA is reported herein. This transformation had a previous design of experiments using the application of a statistical factorial DoE of 4 parameters (nk), where one variable is varied at a time, while others stay constant. The temperature showed the greatest effect on the reaction yield; so, at 298 K the diastereomeric ratio 3:1 of α and ß-epoxides, normally found, was raised to 1:1. Time was the second significant variable, but due to its high correlation with temperature, 30 min were required for a global 90% conversion at least. These diastereoisomers were characterized both isolated and in the mixtures obtained, to determine their antioxidant, antimicrobial and antiproliferative activity, finding a low antioxidant capacity by DPPH, but antimicrobial activity at the level of penicillin in gram negative bacteria by 1ß better to 1α. The antiproliferative capacity was higher for diastereoisomer ß, agreeing with the proportion of the mixture obtained by different conditions, increasing this in relation to the amount of this diastereoisomer present in hormone-dependent cancer cell lines such as Hela, PC-3 and MCF-7, with 10.0 µM obtained values of viability at 21.8 %, 35.8 % and 12.3 % respectively. DoE optimization allows to manipulate the ratio between diastereoisomers with the minimum number of experiments, extending the analysis of the effect of the ratio between diastereoisomers and the in silico potential as well as the biological activity.

Production of encapsulated (25R)-Spirost-5-en-3ß-ol powder with composite coating material and its characterization.

The potential of the (25R)-Spirost-5-en-3ß-ol (diosgenin) is underutilized due to its astringent mouthfeel and aftertaste. To make the consumption more, this research rivets over the use of suitable techniques for encapsulating the diosgenin to use its health benefits for preventing the health disorders. The (25R)-Spirost-5-en-3ß-ol(diosgenin) is gaining popularity in the food market by proving its potential health benefits. This study rivets over the encapsulation of diosgenin due to its high bitter taste which restricts its incorporation in functional foods. Maltodextrin and whey protein concentrates were used as the carrier for encapsulating diosgenin at varying concentrations from 0.1 to 0.5 % and evaluated for powder properties. The optimal conditions were obtained based on the most suited data ranged from the selected properties for the powder. The spray dried 0.3% diosgenin powder produced most suitable properties for powder recovery, encapsulation efficiency, moisture content, water activity, hygroscopicity, and particle size as 51.69-72.18%, 54.51-83.46%, 1.86-3.73%, 0.38-0.51, 10.55-14.08% and 40.38-88.02 µm respectively. The significance of this study relies on the more and better utilization of the fenugreek diosgenin in edible form by masking the bitterness. After encapsulation the spray dried diosgenin is more accessible in powder format with edible maltodextrin and whey protein concentrate. The spray dried diosgenin powder could be a potential agent that fulfils nutritional demands along with protection from some chronic health perturb.

Synthesis of fully functionalized spirostanic 1,2,3-triazoles by the three component reaction of diosgenin azides with acetophenones and aryl aldehydes and their biological evaluation as antiproliferative agents.

Diosgenin is of significant interest due to its biological activity and synthetic application. In this study, we report the synthesis of a series of spirostanic 1,4,5-trisubstituted 1,2,3-triazoles by the three component reaction of (25R)-6-azidospirostan-3,5-diols with acetophenones and aryl aldehydes. The one-pot two step synthesis proceeds through the in situ formation of (E)-chalcones and copper catalyzed reaction with organic azides in DMF medium. Structural diversity was achieved by varying the aldehyde and acetophenone nature as well as the spirostanic azide stereochemistry. The results of in vitro biological assays showed that fully decorated spirostanic 1,2,3-triazoles exerted significant and selective antiproliferative activity against MCF-7, glioblastoma (SNB-19, T98G, A-172) and neuroblastoma (IMR-32, SH-SYSY) (HCT116) cell lines (GI50 in the single-digit micromolar range). The data revealed that benzoyl and aryl substitutions in the triazole ring introduced at the 6ß-position significantly improved the anti-tumor activity of (25R)-6-azidospirostan-3ß,5α-diols. This position on the spirostan core may be the favourable to synthesize of potent anticancer leads from diosgenin.

Recent advances in chemical synthesis, biocatalysis, and biological evaluation of diosgenin derivatives - A review.

Extracting organic compounds from plants and developing derivatives are essential methods for drug discovery. Diosgenin, extracted from Dioscoreaceae plants, is a type of spirostan steroid with various biological effects, including anti-inflammation, neuro-protection, and apoptosis-induction. Many researchers committed their work to the chemical semi-synthesis of diosgenin derivatives to improve diosgenin's therapeutic bioavailability and expand its range of applications in disease treatment and prevention. Biotransformation, a mild whole-cell biocatalysis method, also made crucial contributions to the structural diversity of diosgenin analogs in recent years. Although the structural modification of diosgenin has made significant progress, it lacks a comprehensive review. Here, we review the chemical modification and biotransformation of diosgenin along with the biological evaluation of diosgenin derivatives to provide a reference for the structural modification strategy and pharmaceutical application of diosgenin derivatives.

Dioscin: A review on pharmacological properties and therapeutic values.

Dioscin has gained immense popularity as a natural, bioactive steroid saponin, which offers numerous medical benefits. The growing global incidence of disease-associated morbidity and mortality continues to compromise human health, facilitating an increasingly urgent need for nontoxic, noninvasive, and efficient treatment alternatives. Natural compounds can contribute vastly to this field. Over recent years, studies have demonstrated the remarkable protective actions of dioscin against a variety of human malignancies, metabolic disorders, organ injuries, and viral/fungal infections. The successful usage of this phytocompound has been widely seen in medical treatment procedures under traditional Chinese medicine, and it is becoming progressively prevalent worldwide. This review provides an insight into the wide spectrum of pharmacological activities of dioscin, as reported and compiled in recent literature. The various novel approaches and applications of dioscin also verify the advantages exhibited by plant extracts against commercially available drugs, highlighting the potential of phytochemical agents like dioscin to be further incorporated into clinical practice.

Novel diosgenin-amino acid-benzoic acid mustard trihybrids exert antitumor effects via cell cycle arrest and apoptosis.

In discovering new powerful antitumor agents, two series of novel diosgenin-amino acid-benzoic acid mustard trihybrids (7a-7 g and 12a-12 g) were designed and synthesized. The antiproliferative activities were tested against five human tumor cell lines and one normal cell line using CCK-8 assays. Among the trihybrids, 12e was the most promising compound, which inhibited T24 cells with IC50 value of 6.96 µM, and was stronger than its parent compound diosgenin (IC50 = 32.33 µM). In addition, 12e had weak cytotoxicity on the normal GES-1 cell line (IC50 = 213.74 µM). Moreover, 12e could cause G2/M cell cycle arrest, increase the percentage of apoptosis, induce mitochondrial depolarization, and promote reactive oxygen species generation in T24 cells. Further studies on antitumor mechanism demonstrated that 12e triggered the intrinsic (mitochondrial) and extrinsic (death receptor) apoptotic pathways. More importantly, 12e could inhibit T24 cell proliferation in an in vivo zebrafish xenograft model. Therefore, 12e, as a novel trihybrid with potent cytotoxicity, might be applied as a promising skeleton for antitumor agents, which deserved further optimization.

Synthesis of Demissidine Analogues from Tigogenin via Imine Intermediates.

A five-step transformation of a spiroketal side chain of tigogenin into an indolizidine system present in solanidane alkaloids such as demissidine and solanidine was elaborated. The key intermediate in the synthesis was spiroimine 3 readily obtained from tigogenin by its RuO4 oxidation to 5,6-dihydrokryptogenin followed by amination with aluminum amide generated in situ from DIBAlH and ammonium chloride. The mild reduction of spiroimine to a 26-hydroxy-dihydropyrrole derivative and subsequent mesylation resulted in the formation of 25-epidemissidinium salt or 23-sulfone depending on reaction conditions.

Allosteric modulators enhance agonist efficacy by increasing the residence time of a GPCR in the active state.

Much hope in drug development comes from the discovery of positive allosteric modulators (PAM) that display target subtype selectivity and act by increasing agonist potency and efficacy. How such compounds can allosterically influence agonist action remains unclear. Metabotropic glutamate receptors (mGlu) are G protein-coupled receptors that represent promising targets for brain diseases, and for which PAMs acting in the transmembrane domain have been developed. Here, we explore the effect of a PAM on the structural dynamics of mGlu2 in optimized detergent micelles using single molecule FRET at submillisecond timescales. We show that glutamate only partially stabilizes the extracellular domains in the active state. Full activation is only observed in the presence of a PAM or the Gi protein. Our results provide important insights on the role of allosteric modulators in mGlu activation, by stabilizing the active state of a receptor that is otherwise rapidly oscillating between active and inactive states.

Design and synthesis of novel diosgenin-triazole hybrids targeting inflammation as potential neuroprotective agents.

Alzheimer's disease is a progressive neurodegenerative disease, and its incidence is expected to increase as the global population ages. Recent studies provide increasing evidence that inflammation plays a key role in the pathogenesis and progression of AD. Diosgenin, an active ingredient in Dioscorea nipponica Makino, is a promising bioactive lead compound in the treatment of Alzheimer's disease, which exhibited anti-inflammatory activity. To search for more efficient anti-Alzheimer agents, a series of novel diosgenin-triazolyl hybrids were designed, synthesized, and their neuroprotective effects against oxygen-glucose deprivation-induced neurotoxicity and LPS-induced NO production were evaluated. Most of these new hybrids displayed better activities than DIO. In particular, the promising compound L6 not only demonstrated an excellent neuroprotective effect but also showed the best anti-inflammatory activity. The structure-activity relationship study illustrated that the introduction of benzyl or phenyl triazole did improve the activity, and the introduction of benzyl triazole was better than that of phenyl triazole. The results we obtained showed that the diosgenin skeleton could be a promising structural template for the development of new anti-Alzheimer drug candidates, and compound L6 has the potential to be an important lead compound for further research.

Design, synthesis, and biological evaluation of diosgenin-indole derivatives as dual-functional agents for the treatment of Alzheimer's disease.

The complex pathogenesis of Alzheimer's disease (AD) has become a major obstacle in its treatment. An effective approach is to develop multifunctional agents that simultaneously target multiple pathological processes. Here, a series of diosgenin-indole compounds were designed, synthesized and evaluated for their neuroprotective effects against H2O2 (hydrogen peroxide), 6-OHDA (6-hydroxydopamine) and Aß (beta amyloid) damages. Preliminary structure-activities relationship revealed that the introduction of indole fragment and electron-donating group at C-5 on ring indole could be beneficial for neuroprotective activities. Results indicated that compound 5b was the most promising candidate against cellular damage induced by H2O2 (52.9 ± 1.9%), 6-OHDA (38.4 ± 2.4%) and Aß1-42 (54.4 ± 2.7%). Molecular docking study suggested the affinity for 5b bound to Aß1-42 was -40.59 kcal/mol, which revealed the strong binding affinity of 5b to Aß1-42. The predicted values of brain/blood partition coefficient (-0.733) and polar surface area (85.118 Å2) indicated the favorable abilities of BBB permeation and absorption of 5b. In addition, 5b significantly decreased ROS (reactive oxygen species) production induced by H2O2. In the following in vivo experiment, 5b obviously attenuated memory and learning impairments of Aß-injected mice. In summary, compound 5b could be considered as a promising dual-functional neuroprotective agent against AD.

Influence of Soil Variation on Diosgenin Content Profile in Costus speciosus from Indo-Gangetic Plains.

Costus speciosus is a rich source of commercially important compound Diosgenin, distributed in different regions of India. The present investigation was aimed to quantify diosgenin through High Performance Thin Layer Chromatography in 34 germplasms of Costus speciosus and also to identify the superior sources and to correlate the macronutrients of rhizospheric soil. The starch content varied in microscopic examination and correlated inversely (r=-0.266) with diosgenin content. Findings revealed that the extraction process with acid hydrolysis yielded higher diosgenin content (0.15-1.88 %) as compared to non-hydrolysis (0.009-0.368 %) procedure. Germplasms from Uttar Pradesh (NBCS-4), Jharkhand (NBCS-39) and Bihar (NBCS-2) were identified as elite chemotypes based on hierarchical clustering analysis. The phosphorous content of respective rhizospheric soil correlated positively (r=0.742) with diosgenin content. Findings of present study are useful to identify the new agrotechniques. The elite germplasms can also be used as quality planting material for large scale cultivation in order to assure a sustained supply to the herbal drug industry.

Design and synthesis of diosgenin derivatives as apoptosis inducers through mitochondria-related pathways.

Diosgenin (DSG) has attracted attention recently as a potential anticancer therapeutic agent due to its profound antitumor activity. To better utilize DSG as an antitumor compound, two series of DSG-amino acid ester derivatives (3a-3g and 7a-7g) were designed and synthesized, and their cytotoxic activities against six human cancer cell lines (K562, T24, MNK45, HepG2, A549, and MCF-7) were evaluated. The results obtained showed that a majority of derivatives exhibited cytotoxic activities against these six human tumor cells. Structure-activity relationship analysis revealed that the introduction of l-tryptophan to the C-3 position of DSG and the C-26 position of derivative 5 was the preferred option for these compounds to display significant cytotoxic activities. Among them, compound 7g exhibited significant cytotoxicity against the K562 cell line (IC50 = 4.41 µM) and was 6.8-fold more potent than diosgenin (IC50 = 30.04 µM). Further cellular mechanism studies in K562 cells elucidated that compound 7g triggered mitochondrial-related apoptosis by increasing the generation of intracellular reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP), which was associated with upregulation of the gene and protein expression levels of Bax, downregulation of the gene and protein expression levels of Bcl-2 and activation of the caspase cascade. The above results suggested that compound 7g might be considered a promising scaffold for further modification of more potent anticancer agents.

Preparation, characterization, and cytotoxicity evaluation of self-assembled nanoparticles of diosgenin-cytarabine conjugate.

Diosgenin (DG) isolated from yam roots revealed various bioactivities and applications as drug carrier. In the present study, a conjugate of DG with cytarabine (Ara-C) was used to prepare the self-assembled nanoparticles (NPs) of DG-Ara-C by a nanoprecipitation method. Dynamic light scattering (DLS) as well as transmission electron microscopy (TEM) were employed to analyze the size and the morphology of NPs, respectively. The stability and absorption of DG-Ara-C NPs were measured. Additionally, the cytotoxicity of the NPs was determined via MTT assay. The results indicated that the average particle size of DG-Ara-C NPs was around 190 nm with a narrow size distribution (PDI = 0.1). TEM showed that DG-Ara-C NPs had a spherical morphology. Compared to free DG or Ara-C, the self-assembled DG-Ara-C NPs exhibited a better anti-tumor activity against solid tumor cells as well as leukemia cells. In conclusion, DG possesses dual role in the self-assembled NPs of DG-Ara-C conjugate, being as a promising anticancer drug and drug carrier.

Dioscin and diosgenin: Insights into their potential protective effects in cardiac diseases.

BACKGROUND AND ETHNOPHARMACOLOGICAL RELEVANCE: Dioscin and diosgenin derived from plants of the genus Dioscoreaceae such as D. nipponica and D. panthaica Prain et Burk. Were utilized as the main active ingredients of traditional herbal medicinal products for coronary heart disease in the former Soviet Union and China since 1960s. A growing number of research showed that dioscin and diosgenin have a wide range of pharmacological activities in heart diseases. AIM OF THE STUDY: To summarize the evidence of the effectiveness of dioscin and diosgenin in cardiac diseases, and to provide a basis and reference for future research into their clinical applications and drug development in the field of cardiac disease. METHODS: Literatures in this review were searched in PubMed, ScienceDirect, Google Scholar, China National Knowledge Infrastructure (CNKI) and Web of Science. All eligible studies are analyzed and summarized in this review. RESULTS: The pharmacological activities and therapeutic potentials of dioscin and diosgenin in cardiac diseases are similar, can effectively improve hypertrophic cardiomyopathy, arrhythmia, myocardial I/R injury and cardiotoxicity caused by doxorubicin. But the bioavailability of dioscin and diosgenin may be too low as a result of poor absorption and slow metabolism, which hinders their development and utilization. CONCLUSION: Dioscin and diosgenin need further in-depth experimental research, clinical transformation and structural modification or research of new preparations before they can be expected to be developed into new therapeutic drugs in the field of cardiac disease.