Major Saponins Research Articles

Saponins of North Atlantic Sea Cucumber: Chemistry, Health Benefits, and Future Prospectives

Frondosides are the major saponins (triterpene glycosides) of the North Atlantic sea cucumber (Cucumaria frondosa). Frondosides possess amphiphilic characteristics due to the presence of various hydrophilic sugar moieties and hydrophobic genin (sapogenin). Saponins are abundant in holothurians, including in sea cucumbers that are widely distributed across the northern part of the Atlantic Ocean. Over 300 triterpene glycosides have been isolated, identified, and categorized from many species of sea cucumbers. Furthermore, specific saponins from sea cucumbers are broadly classified on the basis of the fron-dosides that have been widely studied. Recent studies have shown that frondoside-containing extracts from C. frondosa exhibit anticancer, anti-obesity, anti-hyperuricemic, anticoagulant, antioxidant, antimicrobial, antiangiogenic, antithrombotic, anti-inflammatory, antitumor, and immunomodulatory activities. However, the exact mechanism(s) of action of biological activities of frondosides is not clearly understood. The function of some frondosides as chemical defense molecules need to be understood. Therefore, this review discusses the different frondosides of C. frondosa and their potential therapeutic activities in relation to the postulated mechanism(s) of action. In addition, recent advances in emerging extraction techniques of frondosides and other saponins and future perspectives are discussed.

Steroidal saponin profiles and their key genes for synthesis and regulation in Asparagus officinalis L. by joint analysis of metabolomics and transcriptomics

BackgroundAsparagus officinalis L. is a worldwide cultivated vegetable enrichened in both nutrient and steroidal saponins with multiple pharmacological activities. The upstream biosynthetic pathway of steroidal saponins (USSP) for cholesterol (CHOL) synthesis has been studied, while the downstream pathway of steroidal saponins (DSSP) starting from cholesterol and its regulation in asparagus remains unknown.ResultsMetabolomics, Illumina RNAseq, and PacBio IsoSeq strategies were applied to different organs of both cultivated green and purple asparagus to detect the steroidal metabolite profiles & contents and to screen their key genes for biosynthesis and regulation. The results showed that there is a total of 427 compounds, among which 18 steroids were detected with fluctuated concentrations in roots, spears and flowering twigs of two garden asparagus cultivars. The key genes of DSSP include; steroid-16-hydroxylase (S16H), steroid-22-hydroxylase (S22H) and steroid-22-oxidase-16-hydroxylase (S22O-16H), steroid-26-hydroxylase (S26H), steroid-3-β-glycosyltransferase (S3βGT) and furostanol glycoside 26-O-beta-glucosidases (F26GHs) which were correlated with the contents of major steroidal saponins were screened, and the transcriptional factors (TFs) co-expressing with the resulted from synthetic key genes, including zinc fingers (ZFs), MYBs and WRKYs family genes were also screened.ConclusionsBased on the detected steroidal chemical structures, profiles and contents which correlated to the expressions of screened synthetic and TFs genes, the full steroidal saponin synthetic pathway (SSP) of asparagus, including its key regulation networks was proposed for the first time.

Ginsenoside Rh4 inhibits breast cancer growth through targeting histone deacetylase 2 to regulate immune microenvironment and apoptosis

High expression of histone deacetylase 2 (HDAC2) is recognized as a marker of invasive breast cancer (BC). HDAC2 is not only responsible for enhancing tumor cell growth, development, and anti-apoptosis, but also plays a significant role in regulating PD-L1 on the surface of tumor cells. Continuous expression of PD-L1 allows tumor cells to escape immune surveillance. There is not much research on how HDAC2 affects the immune system in breast cancer. Ginsenoside Rh4 (Rh4) is a major rare saponin in heat-treated ginseng, which is widely applied in treating and preventing various diseases because of its potent medicinal value and stable safety. However, it is unclear how Rh4 affects the tumor immune microenvironment in breast cancer. Therefore, this paper aims to investigate the effect of Rh4 on HDAC2 in breast cancer, specifically the effect of HDAC2 on apoptosis and the immune microenvironment to inhibit breast cancer growth. According to our study, ginsenoside Rh4 has been shown to significantly suppress breast cancer cell proliferation without any adverse effects. The molecular docking results of Rh4 and HDAC2 indicate a binding energy of −6.06 kcal/mol, suggesting the potential of Rh4 as a targeting modulator of HDAC2. Mechanistically, Rh4 induces apoptosis of breast cancer cells by the HDAC2-mediated caspase pathway and inhibits the HDAC2-mediated JAK/STAT pathway to regulate the immune microenvironment, which inhibits breast cancer growth. Specifically, Rh4 was shown for the first time to blockade immune checkpoints (PD-1/PD-L1) and increase levels of T-lymphocytes in the tumor. In a word, our study establishes a theoretical framework for applying Rh4 as an immune checkpoint inhibitor as part of breast cancer treatment.

Total Synthesis of Starfish Cyclic Steroid Glycosides. Part 3, Formal Total Synthesis of Luzonicosides A and D

Comprehensive SummaryLuzonicosides A (1) and D (2) are the major saponins isolated from pacific starfish Echinaster Luzonicus, featuring a sterically congested 16‐membered ring which is formed by bridging the C3 and C6 of a 3β,6β‐dihydroxy‐Δ7‐ene steroid with a 1,2‐trans‐linked linear trisaccharide via glycosidic and ether bonds, respectively. Here, we describe a formal total synthesis of starfish cyclic steroid glycosides 1 and 2. The synthetic route is highly modular and versatile, involving construction of the 16‐membered macrocycles via Au(I)‐catalyzed intramolecular glycosylation, highly efficient installation of unsaturated sugar moieties with ortho‐hexynylbenzoates, elaboration of glucuronic acid unit via post‐oxidation, and a de novo synthesis of the ether‐linked pyranose unit.

Biosynthetic Gene Expression and Tissue Distribution of Diosgenin in Dioscorea japonica.

Diosgenin is an aglycone of dioscin, a major bioactive steroidal saponin found in plants, including Himalayan Paris (Paris polyphylla), fenugreek (Trigonella foenum-graecum), and yam (Dioscorea spp.). We have previously demonstrated that a species of natural yam, Dioscorea japonica, contains a promising bioactive compound diosgenin, which induces anti-carcinogenic and anti-hypertriacylglycerolemic activities. Here, we found for the first time that Japanese yam (D. japonica) bulbils are richer in diosgenin than the edible tubers (rhizomes) and leaves. LC-MS and imaging-MS analyses revealed that diosgenin accumulated in the peripheral region of D. japonica bulbils. Additionally, we performed RNA-seq analysis of D. japonica, and multiple sequence alignment identified D. japonica CYP90 (DjCYP90), the orthologous gene of CYP90G4 in P. polyphylla, CYP90B50 in T. foenum-graecum, CYP90G6 in Dioscorea zingiberensis, and CYP90G in Dioscorea villosa, which encodes a diosgenin biosynthetic rate-limiting enzyme. The expression levels of DjCYP90 were significantly upregulated in D. japonica bulbils than in its rhizomes and leaves. Since diosgenin is one of the most promising functional food factors executing several favorable bioactivities, D. japonica bulbils rich in diosgenin would be a beneficial natural resource.

Astragaloside IV inhibits experimental autoimmune encephalomyelitis by modulating the polarization of both microglia/macrophages and astrocytes.

Astragaloside IV (AST IV), a major saponin component and active ingredient isolated from Astragalus membranaceus, has been well known to exhibit neuroprotective effects on diverse models of neurological diseases. Accumulating evidence suggests that dynamic balance of microglia/macrophages and astrocytes plays a vital role in neuroprotection and remyelination. However, dysregulation of microglia/macrophages and astrocytes orchestrate the pathogenesis of nervous system disorders. Therefore, we hypothesized that switching the transformation of microglia/macrophages and astrocytes into the neuroprotective M2 and A2 phenotypes, respectively, could be a potential target for therapeutic intervention. In the present study, we evaluate the efficacy of AST IV intervention on the effects of microglia/macrophages and astrocytes in an experimental autoimmune encephalomyelitis (EAE) model. AST IV improved paralysis and pathology of EAE by inhibiting the neurotoxic M1 microglia/macrophage phenotype, promoting M2 phenotype, shifting astrocytes towards a neuroprotective A2 phenotype, and protecting neurons from apoptosis through inhibition of TLR4/Myd88/NF-kB signalling pathway. Our study showed that AST IV could be a potential and promising drug for multiple sclerosis treatment.

Pharmacokinetics and Oral Bioavailability of Panax Notoginseng Saponins Administered to Rats Using a Validated UPLC–MS/MS Method

Panax notoginseng saponins (PNS) are the most important bioactive components of P. Notoginseng. In this paper, an evaluation of the pharmacokinetics and oral absolute bioavailability of PNS was carried out following intravenous and oral administration of PNS to Sprague-Dawley rats. The plasma concentration of 28 PNS was determined using a validated UPLC-MS/MS system. The results demonstrated that Rb1(32.8%), Rg1(41.4%), R1(9.4%), Re(4.5%), and Rd(3.5%) are the five main ingredients of PNS for administration. After oral administration, it was found that the area under the curve (AUC0-72h) for these five major saponins was significantly different. AUC0-72h of Rb1 and Rd accounted for about 60% of all PNS exposure, while AUC0-72h of Rg1 and R1 only accounted for 0.7%, and Re was undetectable in plasma. Also, PPD, PPT, and CK were detected as the major PNS metabolites in vivo. Furthermore, it was shown that the total oral bioavailability of PNS was only 1.2%.

Enhancing Bioactive Saponin Content of Raphanus sativus Extract by Thermal Processing at Various Conditions.

Pickled radish (Raphanus sativus) is a traditional Asian ingredient, but the traditional method takes decades to make this product. To optimize such a process, this study compared the saponin content of pickled radishes with different thermal processing and traditional processes (production time of 7 days, 10 years, and 20 years) and evaluated the effects of different thermal processes on the formation of radish saponin through kinetics study and mass spectrometry. The results showed that increasing the pickling time enhanced the formation of saponin in commercial pickled radishes (25 °C, 7 days, 6.50 ± 1.46 mg g-1; 3650 days, 23.11 ± 1.22 mg g-1), but these increases were lower than those induced by thermal processing (70 °C 30 days 24.24 ± 1.01 mg g-1). However, it was found that the pickling time of more than 10 years and the processing temperature of more than 80 °C reduce the saponin content. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that the major saponin in untreated radish was Tupistroside G, whereas treated samples contained Asparagoside A and Timosaponin A1. Moreover, this study elucidated the chemical structure of saponins in TPR. The findings indicated that thermal treatment could induce functional saponin conversion in plants, and such a mechanism can also be used to improve the health efficacy of plant-based crops.

Ginsenoside Rb1, a principal effective ingredient of Panax notoginseng, produces pain antihypersensitivity by spinal microglial dynorphin A expression

Panax notoginseng (Chinese ginseng, Sanqi), one of the major ginseng species, has been traditionally used to alleviate different types of chronic pain. The raw P. notoginseng powder is commonly available in China as a non-prescription drug to treat various aliments including arthritic pain. However, strong scientific evidence is needed to illustrate its pain antihypersensitive effects, effective ingredients and mechanism of action. The oral P. notoginseng powder dose-dependently alleviated formalin-induced tonic hyperalgesia, and its total ginsenosides remarkably inhibited neuropathic pain hypersensitivity. Ginsenoside Rb1, the most abundant ginsenoside of P. notoginseng, dose-dependently produced neuropathic pain antihypersensitivity. Conversely, ginsenosides Rg1, Re and notoginseng R1, the other major saponins from P. notoginseng, failed to inhibit formalin-induced tonic pain or mechanical allodynia in neuropathic pain. Ginsenoside Rb1 metabolites ginsenosides Rg3, Compound-K and protopanaxadiol also had similar antineuropathic pain efficacy to ginsenoside Rb1. Additionally, intrathecal ginsenoside Rb1 specifically stimulated dynorphin A expression which was colocalized with microglia but not neurons or astrocytes in the spinal dorsal horn and primary cultured cells. Pretreatment with microglial metabolic inhibitor minocycline, dynorphin A antiserum and specific κ-opioid receptor antagonist GNTI completely blocked Rb1-induced mechanical antiallodynia in neuropathic pain. Furthermore, the specific glucocorticoid receptor (GR) antagonist Dex-21-mesylate (but not GPR30 estrogen receptor antagonist G15) also entirely attenuated ginsenoside Rb1-related antineuropathic pain effects. All these results, for the first time, show that P. notoginseng alleviates neuropathic pain and ginsenoside Rb1 is its principal effective ingredient. Furthermore, ginsenoside Rb1 inhibits neuropathic pain by stimulation of spinal microglial dynorphin A expression following GR activation.

Evaluating the Protective Effect of Ginsenoside Re on Hippocampal Mitochondria in a Rat Model of Vascular Dementia

Vascular dementia (VD) is a common disease among elderly individuals that results in cognitive dysfunction. Although pharmaceutical treatments are used to temporarily improve the symptoms, these have side effects, including mental disorders and epilepsy. Therefore, identifying therapeutic strategies for VD which limit side effects would be advantageous. Previous studies have demonstrated the involvement of oxidative stress in the pathogenesis of VD. As the major saponin type of Panax ginseng, Ginsenoside Re, exerts anti-oxidation and anti-inflammation effects, Re may have a therapeutic role in the management of VD. Our aim was to evaluate this potential therapeutic role of Re in a rat model of VD. We compared mitochondrial function in hippocampal neurons in groups with or without Re administration. Our findings show that Re administration can reverse the effects of VD on mitochondrial structure and function in hippocampal neurons, including protecting against a reduction in the number of mitochondria and preventing mitochondrial vacuolization. The relative expression levels of COX IV and PDH-A1 also increased after Re treatment, with a reduction in mitochondrial H2O2 production, in a time-and dose-dependent manner. These improvements in mitochondrial function protected against VD-associated cognitive dysfunction, measured by performance in a Morris water maze. Based on these findings, we concluded that Ginsenoside Re may ameliorate cognitive impairment in VD by inhibiting mitochondrial oxidative stress in the brain. Collectively, we provide valuable experimental data which could inform the development of safe and effective drugs for the management of VD from ischemia.

A Comprehensive Insight into the Phytochemical, Pharmacological Potential, and Traditional Medicinal Uses of Albizia lebbeck (L.) Benth.

Background Albizialebbeck is a deciduous tree having tremendous medicinal utilities, for example, respiratory, skin, gastrointestinal, oral disorders, eye, urinary, genital, anorectal, inflammatory, and neurological disorders, and venereal diseases. Several studies have been undertaken on the medicinal and traditional values of A. lebbeck. Objective The detailed information about its medicinal uses and pharmacological implications is highly scattered and distributed in different data sources. Hence, the study was conducted to supply an inclusive review of its ethnomedicinal uses, phytochemicals, and the available pharmacological attributes supporting its efficiency in traditional medicine. Method Literature surveys were conducted on this medicinal plant via search engines like Google Scholar, PubMed, and Science Direct, and obtained information up to December 2020 has been assessed and analyzed for this study. Results Systematic investigation revealed that A. lebbeck consists of various phytochemicals, including major alkaloids, flavonoids, saponins, and terpenoids. Its crude extract, fraction, and bioactive compounds exhibited potent adulticidal, antiallergic, anticancer, anticonvulsant, antidiabetic, antidiarrheal, anti-inflammatory, antimicrobial, antinociceptive, antioxidant, antiparasitic, antipyretic, antivenom, estrogenic, neuroprotective, nootropic, ovicidal, and wound healing activities. Conclusions This study proposes that A. lebbeck remains a rich source of phytochemicals with various biological activities which possess outstanding therapeutic benefits to humanity across the world. However, studies are required to estimate the potential side effects. Moreover, mechanistic physiognomies of the isolated compounds with known bioactivities are quite limited; thus, forthcoming research needs to focus on the mechanisms of these active phytochemicals to facilitate their potential enrolling for drug discovery.

Bidesmosidic Triterpenoid Saponins from Wild and Cultivated Gypsophila Paniculata L. (Caryophyllaceae)

Glucuronide oleanane-type triterpenoid carboxylic acid 3, 28-bidesmosides (GOTCAB) of wild and in vivo cultivated Gypsophila paniculata L. roots were assayed by ultra high-performance liquid chromatography coupled with hybrid quadrupole-Orbitrap high resolution mass spectrometry (UHPLCHRMS). More than 20 gypsogenin- and quillaic acid-based GOTCAB saponins were tentatively annotated including isobaric isomers. They are substituted at C-3 with a common 3-O-β-d-galactopyranosyl-(1→2)-[pentosyl-(1→3)]-βd-glucuronopyranoside. C-28 ester-bonded chain is mono- and diacetylated tetra- and pentasaccharide or possesses a methoxycinnamoyl residue. Nine core GOTACBs have not been previously reported in native G. paniculata. The structure of the major saponin of the wild G. paniculata roots was established by 1D and 2D NMR experiments as 3-O-β-d-galactopyranosyl-(1→2)-[β-d-xylopyranosyl-(1→3)]-β-d-glucuronopyranosyl quillaic acid 28-O − α-larabinopyranosyl-(1→4)-α-l-arabinopyranosyl-(1→3)-β-d-xylopyranosyl- (1→4)-α-l-rhamnopyranosyl-(1→2)-β-d-fucopyranosyl ester. For the first time the saponin was isolated from the G. paniculata roots.

Ginsenoside Rg3 attenuates fat accumulation in zebrafish with high-fat-diet-induced obesity

Ginsenoside Rg3 is one of major steroidal saponins in Panax ginseng that has demonstrated several therapeutic effects. In this study, we investigated the effects of ginsenoside Rg3 on lipid accumulation in a high-fat diet (HFD) larval zebrafish model by analyzing fluorescence intensity, total cholesterol (TC), and triglyceride (TG) levels. The effects of ginsenoside Rg3 in a HFD adult zebrafish model were also evaluated on the basis of body length, body weight, body mass index (BMI), hematoxylin–eosin (HE) staining, Oil red staining, quantitative PCR, TC, and TG. In addition, the intestinal bacteria in zebrafish that were capable of metabolizing ginsenoside Rg3 into ginsenoside deglycosylase ginsenoside Rh2 and aglycon ginsenoside deglycosylated protopanaxadiol were measured. Results demonstrated that the fluorescence density of the local trunk in the HFD larval zebrafish model under ginsenoside Rg3 treatment had reduced compared with high cholesterol (HC) group. Moreover, TC levels were significantly lower in the Rg3 treatment group than in the HC group (P < 0.01). However, TG levels did not significantly differ between groups (P > 0.01). In addition, Rg3 could improve the related effects caused by HFD and caused zebrafish body length, body weight, and BMI to approach normal levels. HE and Oil Red O staining of liver revealed the marked accumulation of lipid droplets and histopathological changes in hepatocytes. These changes were attenuated by Rg3 treatment. Rg3 induced the expression of lipid-catabolism-associated and anabolism-associated genes, and the possible mechanism could be attributed to the down-regulation of cholesterol synthesis and up-regulation of cholesterol transport. These results reflected the influence of Rg3 on lipid metabolism and indicated that ginsenoside Rg3 could attenuate fat accumulation and might be a potential agent for preventing obesity.

Platycodin D protects pancreatic β-cells from STZ-induced oxidative stress and apoptosis

Diabetes mellitus is a group of physiological dysfunctions associated with hyperglycemia-mediated oxidative stress and apoptosis in pancreatic β-cells. Platycodin D (PLD) is a major saponin isolated from Platycodon grandiflorum that has been reported to possess many pharmacological effects including anti-oxidative, anti-apoptotic and anti-diabetic. In the present study, we evaluated the effects of PLD on oxidative stress and apoptosis in INS-1 cells exposed to streptozotocin (STZ). Our results showed that PLD improved STZ-caused reduction in cell viability of INS-1 cells. PLD prevented STZ-induced apoptosis in INS-1 cells with decreased bax expression and caspse-3 activity, as well as increased bax expression. PLD decreased ROS production and increased SOD activity in STZ-induced INS-1 cells. Treatment with PLD also improved the insulin secretion capacity and the expression of insulin1/2 in STZ-induced INS-1 cells. Furthermore, PLD suppressed the STZ-induced activation of p38 pathway, while enhanced the activation of Nrf2/HO-1 pathway in INS-1 cells. Treatment with p38 agonist (p79350) or knockdown of Nrf2 reversed the protective effects of PLD on INS-1 cells. Taken together, PLD protects INS-1 cells from STZ-induced oxidative stress and apoptosis. The protective effect of PLD might be ascribed to the regulation of p38 and Nrf2 pathways.

Dereplication of Bioactive Spirostane Saponins from Agave macroacantha.

A dereplication strategy using UPLC-QTOF/MSE, the HMAI method, and NMR spectroscopy led to the identification of five main steroidal saponins (1–5), including three previously unknown compounds named macroacanthosides A–C (3–5), in a bioactive fraction of Agave macroacantha. The major saponins were isolated, and some of them together with the saponin-rich fraction were then evaluated for phytotoxicity on a standard target species, Lactuca sativa. The inhibition values exhibited by the pure compounds were confirmed to be in agreement with the phytotoxicity of the saponin-rich fraction, which suggests that the saponin fraction could be applied successfully as an agrochemical without undergoing any further costly and/or time-consuming purification processes. The NMR data of the pure compounds as well as of those corresponding to the same compounds in the fraction were comparable, which indicated that the main saponins could be identified by means of this replication workflow and that no standards are required.

Terrestrosin D, a spirostanol saponin from Tribulus terrestris L. with potential hepatorenal toxicity

Ethnopharmacological relevanceFructus Tribuli (FT) has been commonly used as a traditional medicine for thousands of years. With the diverse uses of FT, more attention has been paid to its hepatorenal toxicity. However, the compounds causing the hepatorenal toxicity of FT remain undetermined. Terrestrosin D (TED), a major spirostanol saponin isolated from FT, may exert hepatorenal toxicity. Aim of the studyThis study aimed to evaluate the potential hepatorenal toxicity of TED, and preliminarily explore the possible mechanism of TED-induced hepatorenal toxicity. Materials and methodsCytotoxicity assays, a repeated-dose 28-day in-vivo study, a toxicokinetic study, and a tissue distribution study were used to evaluate the potential hepatorenal toxicity of TED. Furthermore, network pharmacology was applied to preliminarily explore the possible mechanism of TED-induced hepatorenal toxicity. ResultsBoth the in vitro and in vivo studies showed that the spirostanol saponin TED had potential hepatorenal toxicity. Nonetheless, hepatorenal toxicity induced by oral treatment with TED at a dosage range of 5 – 15 mg/kg daily for 28 consecutive days to Sprague-Dawley (SD) rats was reversible after 14 days of TED withdrawal. The toxicokinetic study demonstrated that the systematic exposure of SD rats to TED had an accumulation phenomenon and a dose-dependent trend after a 28-day repeated-dose oral administration. The tissue distribution study revealed that TED had a targeted distribution in the liver and kidneys accompanied by a phenomenon of accumulation in SD rats. Network pharmacology combined with molecular docking methods was used to screen for the key targets (HSP90AA1, CNR1, and DRD2) and the key pathways of TED-induced hepatorenal toxicity. ConclusionsThe spirostanol saponin TED, a major spirostanol saponin isolated from FT, had potential hepatorenal toxicity.

The anti-tumor effect of OP-B on ovarian cancer in vitro and in vivo, and its mechanism: An investigation using network pharmacology-based analysis

Ethnopharmacological relevanceMaidong (Liliaceae) is used as a yin-nourishing medication for the treatment of cardiovascular disease, inflammation, and assistant cancer chemotherapy in the clinic. Ophiopogonin B (OP-B), a major saponin extracted from Maidong, is reported to have potential antitumor activities against various human cancers. However, the effects of OP-B on human ovarian cancer (OC) and the potential mechanisms of action are yet elusive.Aim of the study: In this study, we aimed to explore the potential molecular mechanisms of OP-B in the treatment of OC using network pharmacology. In vivo and in vitro experiments were conducted to further verify the therapeutic effects of OP-B on OC. Materials and methodsTo investigate the functions of OP-B against OC holistically, the related targets of OP-B and OC were each predicted based on four public databases. Subsequently, the identified PPI network was constructed to detect the hub potential targets. In addition, GO and KEGG enrichment analysis were applied by Metascape database. Furthermore, we simultaneously investigated the anticancer effects of OP-B on SKOV3 and A2780 human ovarian cancer cells using a cell viability assay, transwell assay, and an image-based cytometric assay. The quantitative real-time PCR and western-blot assay were used to validate the RNA and protein levels of target genes in OP-B treated OC cells. At last, SKOV3-bearing BALB/c nude mice were applied to observe the effectiveness and toxicity of OP-B. ResultsThrough network pharmacological analysis, OP-B was found to play a critical role in OC via multiple targets and pathways, especially the STAT3 signaling pathways. In addition, in vitro experiments found OP-B suppressed SKOV3 and A2780 cells proliferation in a time and concentration dependent manner, and markedly impaired cancer cell migration. Flow cytometry analysis revealed that OP-B significantly increased early and late apoptosis, induced G2/M phase cell cycle arrest in SKOV3 cells and G0/G1 phase cell cycle arrest in A2780 cells. Moreover, OP-B administration down-regulated the expression of p-STAT3 protein, whereas the RNA expression and total protein levels of STAT3 were not altered. Finally, in vivo experiments confirmed the therapeutic effects of OP-B on OC in nude mice with low toxicity in heart, liver, lung, and kidney. ConclusionOP-B could efficiently suppress OC cellular proliferation, migration and induce apoptosis, cell cycle arrest mainly via the regulation of STAT3 signaling pathway. This study provides a promising potential application for an alternative to chemotherapy in ovarian cancer.

Formosanin C attenuates lipopolysaccharide-induced inflammation through nuclear factor-κB inhibition in macrophages.

Extended inflammation and cytokine production pathogenically contribute to a number of inflammatory disorders. Formosanin C (FC) is the major diosgenin saponin found in herb Paris formosana Hayata (Liliaceae), which has been shown to exert anti-cancer and immunomodulatory functions. In this study, we aimed to investigate anti-inflammatory activity of FC and the underlying molecular mechanism. RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) or pre-treated with FC prior to being stimulated with LPS. Thereafter, the macrophages were subjected to analysis of the expression levels of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, as well as two relevant enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The analysis revealed that FC administration blunted LPS-induced production of NO and PGE in a dose-dependent manner, while the expression of iNOS and COX-2 at both mRNA and protein levels was inhibited in LPS-stimulated macrophages pre-treated with FC. Moreover, LPS stimulation upregulated mRNA expression and medium release of TNF-α, IL-1β, and IL-6, whereas this effect was blocked upon FC pre-administration. Mechanistic studies showed that inhibitory effects of FC on LPS-induced inflammation were associated with a downregulation of IκB kinase, IκB, and p65/NF-κB pathway. Taken together, these data suggest that FC possesses an inflammation-suppressing activity, thus being a potential agent for the treatment of inflammation-associated disorders.

Ginsenoside Rh2 upregulates long noncoding RNA STXBP5-AS1 to sponge microRNA-4425 in suppressing breast cancer cell proliferation

BackgroundGinsenoside Rh2, a major saponin derivative in ginseng extract, is recognized for its anticancer activities. Compared to coding genes, studies on long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) that are regulated by Rh2 in cancer cells, especially on competitive endogenous RNA (ceRNA) are sparse. MethodsLncRNAs whose promoter DNA methylation level was significantly altered by Rh2 were screened from methylation array data. The effect of STXBP5-AS1, miR-4425, and RNF217 on the proliferation and apoptosis of MCF-7 breast cancer cells was monitored in the presence of Rh2 after deregulating the corresponding gene. The ceRNA relationship between STXBP5-AS1 and miR-4425 was examined by measuring the luciferase activity of a recombinant luciferase/STXBP5-AS1 plasmid construct in the presence of mimic miR-4425. ResultsInhibition of STXBP5-AS1 decreased apoptosis but stimulated growth of the MCF-7 cells, suggesting tumor-suppressive activity of the lncRNA. MiR-4425 was identified to have a binding site on STXBP5-AS1 and proven to be downregulated by STXBP5-AS1 as well as by Rh2. In contrast to STXBP5-AS1, miR-4425 showed pro-proliferation activity by inducing a decrease in apoptosis but increased growth of the MCF-7 cells. MiR-4425 decreased luciferase activity from the luciferase/STXBP5-AS1 construct by 26%. Screening the target genes of miR-4425 and Rh2 revealed that Rh2, STXBP5-AS1, and miR-4425 consistently regulated tumor suppressor RNF217 at both the RNA and protein level. ConclusionLncRNA STXBP5-AS1 is upregulated by Rh2 via promoter hypomethylation and acts as a ceRNA, sponging the oncogenic miR-4425. Therefore, Rh2 controls the STXBP5-AS1/miR-4425/RNF217 axis to suppress breast cancer cell growth.

Kochia scoparia Saponin Momordin Ic Modulates HaCaT Cell Proliferation and Apoptosis via the Wnt/β-Catenin Pathway.

Psoriasis is a chronic, recurrent, immunoinflammatory disease. For a long period, Traditional Chinese Medicine (TCM) is considered a reliable alternative therapy for patients with psoriasis. Fructus Kochiae (or Kochia scoparia) and its principle saponin, Momordin Ic, have been reported to protect against inflammation. Herein, we demonstrated that Momordin Ic could inhibit HaCaT cell proliferation and enhance cell apoptosis. In the meantime, Momordin Ic alters Wnt/β-catenin pathway activation by affecting β-catenin nuclear distribution. The Wnt/β-catenin signaling activator LiCl partially reversed the effects of Momordin Ic on HaCaT phenotypes and the Wnt/β-catenin pathway factors. Altogether, we demonstrate the inhibitory effects of Momordin Ic, one of the major saponin constituents of Fructus Kochiae, on HaCaT cell proliferation and Momordin Ic-induced alteration within the Wnt/β-catenin pathway. Momordin Ic might act on HaCaT cells by modulating the Wnt/β-catenin pathway.