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A natural antioxidant-emulsifier was developed from oil pressed Pistacia lentiscus fruit and tested for oil-in-water nanoemulsions ?-carotene encapsulation. Five extracts were prepared, characterized and screened for their emulsifying capacity. The extract prepared with 75% ethanol (Ex-75%), displayed the highest antioxidant capacity (EC50 = 4.6 +- 0.2�mg/mL), which was significantly correlated with saponin and polyphenol contents (F = 22.30; P-value = 0.018). Under the same high-pressure homogenization conditions, Pistacia Ex-75% and the synthetic emulsifier (Tween-80) produced a comparable physically stable ?-carotene-rich nanoemulsions with d4,3 of 163.4 +- 2.5 and 158.4 +- 4�nm, respectively, and a similar monomodal size distribution following 90�days of storage at 25� C. However, Pistacia Ex-75% markedly improved the chemical stability of encapsulated ?-carotene during the storage period at both 5 and 25� C. These results suggest that Pistacia Ex-75% is effective as an antioxidant-emulsifier and could be used as a dual-purpose functional ingredient in emulsified products. 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. This work was carried out in the framework of the contract program project for Laboratory of Environmental Bioprocesses at Center of Biotechnology of Sfax supported by the Ministry of Higher Education and Scientific Research-Tunisia (LR15CBS01) and the JICA-JST Science and Technology Research Partnership for Sustainable Development (SATREPS) Project: "Valorization of Bio-resources based on Scientific Evidence in Semi- and Arid Land for Creation of New Industry" (grant number: JPMJSA1506). Authors are grateful for the Ministry of Higher Education and Scientific Research (MESRS) Tunisia and Japan International Cooperation agency (JICA) and Japan Science and Technology agency (JST) for the financial support. Authors would like to thank Mr. Sofian Boukataya for supplying the Pistacia lentiscus fruits and helping with their pressing. Scopus

Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines, especially Vernonia amygdalina, a famous nature medicine for the treatment of tonsillitis, diabetes, pneumonia. The current study was designed to combine molecular networking (MN) with diagnostic ions for rapid identification of Δ

Osteosarcoma (OS) is a highly metastatic bone cancer that usually affects children. Rhizoma Paridis saponins (RPS) have been identified to show a broad-spectrum anti-tumor activity. Our previous study has identified vasculogenic mimicry (VM) as an indicator of poor prognosis for OS. Rhizoma Paridis ethanol extract exhibits potent anti-OS property. However, the anti-metastatic effect of RPS on OS and the detailed mechanisms remain unknown. RPS was characterized by liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOF/MS) analysis. The anti-OS, anti-metastasis and anti-VM activities of RPS were investigated using in vitro biological assays and a xenograft mouse model. Western blot, qRT-PCR, ELISA, Phalloidin staining and immunohistochemistry assays were conducted to investigate the molecular mechanism of RPS. A total of 34 phytochemicals from RPS were identified by LC/Q-TOF/MS. RPS dose-dependently suppressed the OS cell proliferation, metastasis and VM formation in vitro and in vivo. Mechanically, we found that RPS downregulated migration-inducing gene 7 (MIG-7) expression, resulting in inhibition of the PI3K/MMPs/Ln-5γ2 pathway and cell protrusion formation. Additionally, we confirmed that RPS downregulated MIG-7 by upregulating miR-520d-3p expression. Our results suggests that RPS inhibits the VM formation and metastasis of OS by modulating the miR-520d-3p/MIG-7 signaling axis.

Background: Upregulation of mitochondrial E3 ubiquitin ligase 1 (Mul1) contributes to brain injury in ischemic stroke due to disturbance of mitochondrial dynamics, and bioinformatics analysis predicts that Mul1 is a potential target of Dipsacoside B. Objective: The aim of the study was to explore whether Dipsacoside B can exert a beneficial effect on brain injury in the ischemic stroke rat via targeting Mul1. Methods: The SD rat brains or PC12 cells were subjected to 2 h-ischemia or 8 h-hypoxia plus 24 h-reperfusion or 24 h-reoxygenation to establish the ischemic stroke rat model in vivo or in vitro, which were treated with Dipsacoside B at different dosages. The brain or PC12 cell injury, relevant protein levels and mitochondrial functions were measured by methods of biochemistry, flow cytometry or Western blot. Results: The neurological dysfunction and brain injury (such as infarction and apoptosis) observed in the ischemic stroke rats were accompanied by increases in Mul1 and dynamin-related protein 1 (Drp1) levels along with decreases in mitofusin 2 (Mfn2) level and ATP production. These effects were attenuated by Dipsacoside B. Consistently, cell injury (necroptosis and apoptosis) occurred in the PC12 cells exposed to hypoxia concomitant with the upregulation of Mul1 and Drp1 along with downregulation of Mfn2 and mitochondrial functions (such as increases in reactive oxygen species production and mitochondrial fission and decreases in mitochondrial membrane potential and ATP production).These phenomena were reversed in the presence of Dipsacoside B. Conclusion: Dipsacoside B can protect the rat brain against ischemic injury via inhibition of Mul1 due to the improvement of mitochondrial function.

Polyphyllin II (PPII) is a steroidal saponin isolated fromTo explore whether PPII induce autophagy and the relationship between autophagy and apoptosis in non-small cell lung cancer (NSCLC) cells.The effects of PPII (0, 1, 5, and 10 μM) were elucidated by CCK8 assay, colony formation test, TUNEL staining, MDC method, and mRFP-GFP-LC3 lentivirus transfection in A549 and H1299 cells for 24 h. DMSO-treated cells were selected as control. The protein expression of autophagy (LC3-II, p62), apoptosis (Bcl-2, Bax, caspase-3) and p-mTOR was detected by Western blotting. We explored the relationship between autophagy and apoptosis by autophagy inhibitor CQ (10 μM) and 3-MA (5 mM).PPII (0, 1, 5, and 10 μM) inhibited the proliferation and induced apoptosis. The ICPPII-induced apoptosis exerts its anticancer activity by inhibiting autophagy, which will hopefully provide a prospective compound for NSCLC treatment.

Drug-resistant bacterial infections pose a serious threat to human public health. Biofilm formation is one of the main factors contributing to the development of bacterial resistance, characterized by a hypoxic and microacidic microenvironment. Traditional antibiotic treatments have been ineffective against multidrug-resistant (MDR) bacteria. Novel monotherapies have had little success. On the basis of the photothermal effect, molybdenum disulfide (MoSsub2/sub) nanoparticles were used to link quaternized polyethylenimine (QPEI), dihydroporphyrin e6 (Ce6), andiPanax notoginseng/isaponins (PNS) in a zeolitic imidazolate framework-8 (ZIF-8). A multifunctional nanoplatform (MQCP@ZIF-8) was constructed with dual response to pH and near-infrared light (NIR), which resulted in synergistic photothermal and photodynamic antibacterial effects. The nanoplatform exhibited a photothermal conversion efficiency of 56%. It inhibited MDRiEscherichia coli/i(iE. coli/i) and MDRiStaphylococcus aureus/i(iS. aureus/i) by more than 95% and effectively promoted wound healing in mice infected with MDRiS. aureus/i. The nanoplatform induced the death of MDR bacteria by promoting biofilm ablation, disrupting bacterial cell membranes and intracellular DNA, and interfering with intracellular material and energy metabolism. In this study, a multifunctional nanoplatform with good antibacterial effect was developed. The molecular mechanisms of MDR bacteria were also elucidated for possible clinical application.

To determine the effects of astragaloside IV on cerebral ischemic-reperfusion injury in rats and to explore underlying mechanisms of brain protection.Sixty Sprague-Dawley rats were randomized into four groups: Sham, cerebral ischemia-reperfusion (I/R group), I/R+astragaloside IV (I/R+AST-IV group) and I/R+astragaloside IV+PKA kinase inhibitor H-89 (I/R+AST-IV+H-89 group). All I/R rats were subjected to 2 h cerebral ischemia, followed by 24 h reperfusion and scored for neurobehavior. Cerebral infarct volume, pathomorphological changes and brain apoptosis, in addition to changes in expression of Cx36, PKA, Bax and Bcl-2 proteins, were assessed.Astragaloside IV treatment reduced neurobehavioral score and percentage volume of cerebral infarct, reducing pathomorphological injury and brain apoptosis. Expressions of Cx36 and PKA protein were increased and the Bax/Bcl-2 ratio decreased. All astragaloside IV effects were reversed by the PKA inhibitor and H-89.Astragaloside IV attenuated cerebral I/R injury in rats by increasing Cx36 and PKA protein expression and reducing the Bax/Bcl-2 ratio.

Jujuboside B (JB) found in the seeds of Zizyphi Spinosi Semen possesses pharmacological functions, such as anti-inflammatory, antiplatelet aggregation, and antianxiety potentials. This study evaluated the effect of JB on liver failure in cecal ligation and puncture (CLP)-induced sepsis. First, we observed histopathological changes in the liver by optical microscopy and the activity of enzymes in serum such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We further measured the levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, nitric oxide (NO), and antioxidative parameters in liver homogenate. The expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), and glucocorticoid receptor (GR) in the liver was observed by Western blotting. CLP enhanced the migration of inflammatory cells, ALT and AST concentrations, and necrosis, which were reduced by JB. In addition, JB reduced 11β-HSD2 expression and levels of inflammatory mediators (TNF-α, IL-1β, and NO) in the liver, increased GR expression, enhanced endogenous antioxidative capacity. These results further suggest that JB may protect the liver against CLP-induced damage by regulating anti-inflammatory responses, downregulating 11β-HSD2 expression and antioxidation, and up-regulating GR expression.

Multiple myeloma (MM) is an incurable plasma cell malignancy associated with poor survival. Novel therapeutic drugs are urgently needed to improve MM therapy and patient outcomes. This study aimed to investigate the effect of formosanin C (FC), a Chinese medicine monomer, on MM in vitro and disclose the underlying molecular mechanism. The effect of FC on the viability, proliferation, apoptosis, and autophagy of MM cell lines (NCI-H929 and ARP1) was studied through CCK-8, colony formation, flow cytometry, GFP-LC3, and western blotting assays, respectively. A pharmacological approach and network pharmacology technology were implemented to explore the potential mechanisms of the action of FC on MM cells. FC efficiently suppressed the viability and colony-forming capacity, but promoted the number of autophagic vacuoles with GFP-LC3 localization and the percentage of apoptotic cells in MM cells. Additionally, FC significantly increased the levels of the autophagy-related proteins LC3-Ⅱ and Beclin 1, as well as the apoptosis-related proteins Bax and cleaved caspase-3, but blocked the expression of the proapoptotic protein Bcl-2 in the cells; these effects were reversed by an inhibitor of autophagy, 3-methyladenine. What's more, we found that the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was involved in the FC-mediated inhibition of MM. Pharmacological inhibition of this pathway dramatically relieved FC-triggered excessive expression of autophagy-related proteins and rescued MM cells from FC-induced apoptosis. Our findings indicate that FC exhibits an anti-MM effect by activating cell autophagy through the PI3K/AKT/mTOR signaling pathway.

Cardiac fibrosis is a common precursor of ventricular dysfunction and heart failure. We investigated the role of oxidative stress in myocardial fibrosis and the protective effect of panaxatriol saponin (PTS) against myocardial infarction (MI)-induced cardiac fibrosis and explored the underlying mechanisms. In vitro, cell viability was tested using a cell counting kit. The reactive oxygen species (ROS) levels including hydrogen peroxide (H

Dioscorea zingiberensis is a valuable medicinal herb rich in steroidal saponins. To reveal the role of jasmonic acid (JA) on physiology and steroidal saponins accumulation, D. zingiberensis were treated with different concentrations of JA. The antioxidant capacity, photosynthetic parameters, fatty acids and metabolites related to steroidal saponins biosynthesis (phytosterols, diosgenin and steroidal saponins) were examined under JA treatment. The results demonstrated that JA treatment caused a great reduction in MDA, stomatal width, photosynthetic rate and photosynthetic pigment, induced a considerable increase in proline, soluble sugar, soluble protein and antioxidant enzymes (CAT, POD and SOD), and leaded to a significant up-regulation in the expression of genes related to antioxidant system and chlorophyll degradation. Specialized metabolites displayed various changes under different concentrations of JA. The majority of fatty acids exhibited negative responses to JA treatment in leaf and rhizome. In leaf, JA treatment enhanced the accumulation of phytosterols and diosgenin, but decreased the accumulation of steroidal saponins. However, steroidal saponins were mainly accumulated in rhizome and were highly increased by JA treatment. Redundancy analysis illustrated that fatty acids were strongly associated with metabolites related to steroidal saponins. Among all fatty acids, C16:0, C18:1, C18:3, C22:0 and C24:0 contributed most to the variation in metabolites related to steroidal saponin biosynthesis. Overall, JA treatment leaded to an increase in steroidal saponins, but an inhibition of plant growth. Thus, the negative effects of JA application on plant physiology should be carefully assessed before being utilized to increase the production of steroidal saponins in D. zingiberensis.

The sea cucumber Apostichopus japonicus is one of the most dominant and economically important aquaculture species in China. Saponin, which possesses notable biological and pharmacological properties, is a key determinant of the nutritional and health value of A. japonicus. In the present study, we amplified the full-length cDNA of a phosphomevalonate kinase (PMK) gene (named AjPMK) using rapid amplification of cDNA ends (RACE). Subsequently, we engineered a recombinant AjPMK (rAjPMK) protein and assessed its enzymatic activity by enzyme-linked immunosorbent assay (ELISA). Proteins that interact with rAjPMK were screened and identified via pull-down assay combined with liquid chromatography with tandem mass spectrometry (LC-MS/MS). We found that the full-length cDNA of AjPMK contained 1354 bp and an open reading frame (ORF) of 612 bp. The AjPMK protein was predicted not to contain a signal peptide but to contain a phosphonolate kinase domain seen in higher eukaryotes and a P-loop with a relatively conserved nucleoside triphosphate hydrolase domain. The molecular weight of the AjPMK protein was estimated to be 23.81 kDa, and its isoelectric point was predicted to be 8.72. Phylogenetic analysis showed that AjPMK had a closer evolutionary relationship with genes from starfish than with those of other selected species. Besides, we found that rAjPMK synthesized mevalonate-5-diphosphate, interacted either directly or indirectly with crucial pattern recognition receptors (PRRs) and was regulated by immune-related processes, including antioxidative reactions, stress resistance responses and enzyme hydrolysis. Moreover, AjPMK also interacted with farnesyl pyrophosphate synthase, an enzyme reported to be involved in saponin biosynthesis. Together, our findings implied that AjPMK may be directly involved in saponin biosynthesis and the regulation of various innate immune processes.

The aim of this study was to investigate the antidepressant effect of Jujuboside A (JuA) on corticosterone (CORT)-induced depression in mice and explore the underlying mechanisms.The mice models were submitted to CORT and treated with JuA (10 and 30 mg/kg) for three weeks. Experiments were also performed on mice with brain-derived neurotrophic factor knockdown (BDNF (±)) as control subjects. Behavioral tests, including the open field test (OFT), tail suspension test (TST), forced swimming test (FST) and Morris water maze (MWM), were then performed to evaluate the antidepressant effect of JuA. The expression levels of BDNF, tyrosine kinase receptor B (TrkB), and cyclic AMP response element binding protein (CREB) in the hippocampi of mice were examined by immunohistochemistry (IHC) and Western blot. The effect of JuA on the viability of mouse hippocampal cells (HT22) was also assessed by CCK-8 assay.JuA significantly decreased the OFT and TST immobility time of the mice, the total distance travelled and the time spent in the central area also effectively increased in the OFT. In the MWM, the escape latencies of the mice decreased remarkably, while the number of times the mice crossed the platform and the target quadrant increased significantly after treatment with JuA. In addition, the BDNF, TrkB, and CREB expression levels were significantly increased in the hippocampi of the mice treated with JuA. Furthermore, JuA clearly attenuated CORT-induced cell injury, as evidenced by the increased viability of the HT22 cells.These findings demonstrated that JuA may exhibit potential antidepressant effect in mice by increasing protein expression levels of BDNF, TrkB, CREB, and improving the viability of the hippocampal cells.

Furunculosis caused by Aeromonas salmonicida in turbot farming is increasingly leading to huge economic losses. In this study, an inactivated vaccine containing a compound adjuvant of ginseng stem leaf saponins and aluminum hydroxide gel (GSLS/Alum) was developed against A. salmonicida and evaluated on turbot. As a result, serum antibody titer in vaccinated group was significantly higher than that in control group and the relative percentage survival (RPS) was up to 75.7%. Comparatively, the RPS of groups that vaccinated with only inactivated vaccine and vaccine containing Alum adjuvant or an oil emulsion Montanide™ ISA 763A were 32.4%, 48.6% and 64.9%, respectively. Although the vaccine containing oil adjuvant elicited comparable IgM level as that containing the compound GSLS/Alum adjuvant, the latter had no obvious side effects. Moreover, the inactivated vaccine containing the compound adjuvant was more likely to induce a higher cellular immune response according to the expressions of some immune related genes. Most importantly, an excellent protection of the vaccine containing GSLS/Alum adjuvant was obtained when turbots were naturally infected under clinical condition. In summary, our study demonstrated that the formulation of GSLS and Alum is a potential compound adjuvant in turbot vaccine development.

Some of the most effective anticancer compounds are still derived from plants since the chemical synthesis of chiral molecules is not economically efficient. Rapid discovery of lead compounds with pronounced biological activity is essential for the successful development of novel drug candidates. This work aims to present the chemical diversity of antitumor bioactive compounds and biotechnological approaches as alternative production and sustainable plant biodiversity conservation. Astragalus spp., (Fabaceae) and Gloriosa spp. (Liliaceae) are selected as research objects within this review because they are known for their anticancer activity, because they represent two of the largest families respectively in dicots and monocots, and also because many of the medicinally important plants are rare and endangered. We summarized the ethnobotanical data concerning their anticancer application, highlighted the diversity of their secondary metabolites possessing anticancer properties such as saponins, flavonoids, and alkaloids, and revealed the potential of the in vitro cultures as an alternative way of their production. Since the natural supply is limited, it is important to explore the possibility of employing plant cell or organ in vitro cultures for the biotechnological production of these compounds as an alternative.

The ginsenoside Rh2 (Rh2) is a saponin of medicinal ginseng, and it has attracted much attention for its pharmacological activities. In this study, we investigated the interaction of Rh2 with biological membranes using model membranes. We examined the effects of various lipids on the membrane-disrupting activity of Rh2 and found that cholesterol and sphingomyelin (SM) had no significant effect. Furthermore, the effects of Rh2 on acyl chain packing (DPH anisotropy) and water molecule permeability (GP

Roots of Platycodon grandiflorus A. De Candolle (Campanulaceae), with the bark removed, have been used as food and frequently employed as herbal medicines for inflammatory diseases such as tonsillitis, dermatitis, and cough. Platycodins are the bioactive saponin components of these crude medicines. Recently, P. grandiflorus have been cultivated in Japan and are harvested from October to December according to conventional practices. Seasonal fluctuations in the total saponin content of these roots were determined using LC/MS methods to recommend harvesting times when the saponin content is high. Platycodins A and C are monoacetylated forms of platycodin D; however, the acetyl form is unstable and deacetylates easily. Here, the contents of platycodin D, platycodin D

The objective of study was to find the actions of astragaloside IV (ASIV) on PAH due to monocrotaline (MCT) in rats. Intraperitoneal injection of 60 mg/ kg MCT was injected to rats, come after by ASIV treatment with doses of 10 mg/kg daily once or 30 mg/kg of dose for twenty one days once daily. RVSP, serum inflammatory cytokines, RVH, and the other pathological parameters of the pulmonary arteries were evaluated. ASIV attenuated the increased pulmonary artery pressure and its structure in rat modification due to MCT. Additionally, ASIV avoided the rise in tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels in the blood serum, and their expression of gene in the pleural parts, which was caused by MCT. ASIV promoted apoptotic resistance of HPASMCs and weakened the hypoxia-induced proliferation. ASIV shows over expression of caspase-3, caspase-9, p21, p27, and Bax, while ASIV downregulated Bcl-2, phospho-ERK, HIF-1α, and protein appearance in HPASMCs. These findings of the in vitro and the in vivo experiment indicate that astragaloside IV exerts protective effects against pulmonary arterial pressure, and may have action to be improved into pharmacological drug for pulmonary arterial pressure treatment.

Vascular endothelial cells and oxidation reduction system play an important role in the pathogenesis of atherosclerosis (AS). If these conditions are disordered, it will inevitably lead to plaque formation and even rupture. Astragaloside IV (AsIV) and salvianolic acid B (Sal B) are the main active ingredients of Astragalus membranaceus and Salvia miltiorrhiza, respectively, and found to ameliorate vascular endothelial dysfunction and protect against oxidative stress in recent studies. However, it is still unknown if the combination of AsIV and Sal B (AsIV + Sal B) can inhibit the development of plaque through amplifying the protective effect of vascular endothelial cells and anti-oxidative stress effect. To clarify the role of AsIV + Sal B in AS, we observed the efficacy of each group (Control, Model, AsIV, Sal B, and AsIV + Sal B) by biomolecular assays, such as observing the pathological morphology of the aorta by oil red O staining, evaluating the level of oxidative stress and endothelial cells in the serum by the Elisa test, and analyzing the changes of all small molecule metabolites in liver tissue by UPLC-QTOF-MS. Results showed that AsIV, Sal B and AsIV + Sal B decreased the deposition of lipid in the arterial wall, so as to exert the effect of anti-oxidant stress and vascular endothelial protection, where the inhibitory effect of AsIV + Sal B was the most obvious. Metabonomics analysis showed that Sal B regulated the metabolic pathways of arginine and proline. AsIV regulated glycerol metabolism and saturated fatty acid biosynthesis metabolism. AsIV + Sal B is mainly related to the regulation of the citrate cycle (TCA cycle), alanine, aspartic acid, and glutamate metabolism, cysteine, and methionine metabolism. Succinic acid and methionine are synergistic metabolites that exert an enhancing effect when AsIV and Sal B were used in combination. In conclusion, we demonstrated that AsIV acompanied with Sal B can be successfully used for anti-oxidative stress and vascular endothelial protection of AS, and succinic acid and methionine are the synergistic metabolites.

Ischaemic stroke is a common neurological disease and a leading cause of severe disability and death in developed countries. In most cases, stroke is thought to be a multifactorial disorder or complex trait for which classic patterns of inheritance cannot be shown. Xuesaitong is one of the most commonly used medicines for treating ischemic stroke in China. However, compared to the conventional therapy, the effectiveness and safety of Xuesaitong for ischemic stroke needs to be further systematically reviewed and determined.Relevant randomized controlled trials (RCTs) examining the use of the Xuesaitong soft capsule in the treatment of patients with ischemic stroke were identified from databases, including the China National Knowledge Infrastructure, Wanfang, PubMed, Embase, and Web of Science databases. Next, 2 researchers independently extracted information from the included studies, analyzed the data using STATA 15.0 software, and evaluated the quality of the included studies using RevMan 5.3.A total of 17 RCTs (comprising 1,942 patients with ischemic stroke) were included in the meta-analysis. The meta-analysis results showed that the Xuesaitong soft capsule treatment increased patients' total effective rate compared to conventional or other drug treatments, and improved patients' Clinical Severity Score (CSS scores) or Barthel index (BI) score. A further subgroup analysis stratified by different treatment times showed that Xuesaitong soft capsule treatment at 4 and 8 weeks improved CSS scores more than treatment at 2 weeks in patients with ischemic stroke. Additionally, the Xuesaitong soft capsule also significantly improved plasma viscosity, whole-blood viscosity at high and low shear rates, fibrinogen, hematocrit, and the effect on traditional Chinese medicine (TCM) single symptoms or signs in patients with ischemic stroke.In summary, compared to conventional or other drug treatments, the Xuesaitong soft capsule treatment was beneficial in improving patients' TCM symptoms (e.g., crooked mouth and tongue, and dizziness) and various indicators. Further, Xuesaitong soft capsule may be a safe and effective drug for the treatment of ischemic stroke. And large-scale randomized clinical trials are needed to further confirm our findings.

This study investigated different gut bacteria in an anaerobic environment to identify specific candidates that could transform astragaloside IV (AIV) to cycloastragenol (CA). Two representative gut microbes, lactic acid bacteria (LAB) and bifidobacteria, could metabolize AIV to CA. Multiple screenings showed two metabolic pathways to metabolize AIV in two groups of bacteria. LAB metabolized AIV initiated by removing the C-6 glucose, whereas bifidobacteria indicated the initial removal of C-3 xylose. The final products differed between the two groups as bifidobacteria showed the production of CA, whereas LAB demonstrated preferential production of 20R, 24S-epoxy-6α, -16β, -25-trihydroxy-9, -19-cycloartan-3-one (CA-2H).

Recently, necroptosis has emerged as one of the important mechanisms of ischemia stroke. Necroptosis can be rapidly activated in endothelial cells to cause vascular damage and neuroinflammation. Panax notoginseng saponins (PNS), an ingredient extracted from the root of Panax notoginseng (Burk.) F.H. Chen, was commonly used for ischemic stroke, while its molecular mechanism and targets have not been fully clarified. Our study aimed to clarify the anti-necroptosis effect of PNS by regulating RIP1-RIP3-MLKL signaling pathway in brain microvascular endothelial cells (BMECs) subjected to transient oxygen-glucose deprivation (OGD/resupply [R]). In vitro, the necroptosis model of rat BMECs was established by testing the effect of OGD/R in the presence of the pan-caspase inhibitor z-VAD-FMK. After administration of PNS and Nec-1, cell viability, cell death modality, the expression of RIP1-RIP3-MLKL pathway and mitochondrial membrane potential (Δψm) level were investigated in BMECs upon OGD/R injury. The results showed that PNS significantly enhanced cell viability of BMECs determined by CCK-8 analysis, and protected BMECs from necroptosis by Flow cytometry and TEM. In addition, PNS inhibited the phosphorylation of RIP1, RIP3, MLKL and the downstream expression of PGAM5 and Drp1, while similar results were observed in Nec-1 intervention. We further investigated whether PNS prevented the Δψm depolarization. Our current findings showed that PNS effectively reduced the occurrence of necroptosis in BMECs exposed to OGD/R by inhibition of the RIP1-RIP3-MLK signaling pathway and mitigation of mitochondrial damage. This study provided a novel insight of PNS application in clinics.

To evaluate the efficacy of deep vein thrombosis (DVT) prevention among real-world surgical inpatients who received panax notoginseng saponins (PNS) combined with low-molecular-weight heparin (LMWH).A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital, Capital Medical University, Beijing, China. Participants received LMWH alone or PNS combined with LMWH for preventing DVT. The primary outcome was incidence of lower extremity DVT, which was screened once a week. Participants in the LMWH group were given LMWH (enoxaparin) via hypodermic injection, 4000-8000 AxalU once daily. Participants in the exposure group received PNS (Xuesaitong oral tablets, 100 mg, 3 times daily) combined with LMWH given the same as LMWH group.Of the 325 patients screened for the study, 281 participants were included in the final analysis. The cohort was divided into PNS + LMWH group and LMWH group with 134 and 147 participants, respectively. There was a significant difference of DVT incidence between two groups (P=0.01), with 21 (15.7%) incident DVT in the PNS + LMWH group, and 41 (27.9%) incident DVT in the LMWH group. Compared with participants without DVT, the participants diagnosed with DVT were older and had higher D-dimer level. The multivariate logistic regression model showed a significant lower risk of incident DVT among participants in the PNS + LMWH group compared with the LMWH group (odds ratio 0.46, 95% confidence interval, 0.25-0.86). There were no significant differences in thromboelaslography values (including R, K, Angle, and MA) and differences in severe bleeding between two groups. No symptomatic pulmonary embolism occurred during the study.Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy, without increased risk of bleeding.

Production losses of olive flounder (Paralichthys olivaceus) have increased owing to viral haemorrhagic septicaemia virus (VHSV) infection. In this study, we determined safe concentrations of orally administered saponin and chitosan by analysing serum enzyme (AST/ALT) levels as biochemical markers of hepatic injury. Furthermore, we demonstrated the efficacy, duration of protection, and safety of saponin and chitosan-based vaccines with inactivated VHSV (IV). Oral administration of saponin, chitosan, and their combination did not induce fish mortality at all tested concentrations (0.29, 1.45, and 2.9 mg/g of fish body weight/day) 10 days after administration. However, AST level was high at a dose0.29 mg/g of fish body weight/day. Both saponin and chitosan were found to be safe and acceptable for vaccination studies at a dose of 0.29 mg/g of fish body weight/day. Administration of IV alone did not induce protection at 2 and 4 weeks post vaccination (wpv). Olive flounders administered saponin + IV and chitosan + IV vaccines had higher immunity against VHSV with relative percentage survival (RPS) of 12.5-7.5% and 0-20.1%, respectively; however, additional immunisation with combination of saponin + chitosan + IV clearly enhanced the protection with RPS values of 10-15%, 26.7%, 42.9%, and 37.5% at 4, 8, 12, and 20 wpv, respectively. Although the RPS value of oral immunisation was not comparable to that of injectable vaccines, the manufacturing process is simple and oral administration causes less stress to juvenile fish. To investigate the development of a protective immune response, olive flounder were re-challenged with VHSV (10

Soft-bodied slow-moving sea creatures such as sea stars and sea cucumbers lack an adaptive immune system and have instead evolved the ability to make specialized protective chemicals (glycosylated steroids and triterpenes) as part of their innate immune system. This raises the intriguing question of how these biosynthetic pathways have evolved. Sea star saponins are steroidal, while those of the sea cucumber are triterpenoid. Sterol biosynthesis in animals involves cyclization of 2,3-oxidosqualene to lanosterol by the oxidosqualene cyclase (OSC) enzyme lanosterol synthase (LSS). Here we show that sea cucumbers lack LSS and instead have two divergent OSCs that produce triterpene saponins and that are likely to have evolved from an ancestral LSS by gene duplication and neofunctionalization. We further show that sea cucumbers make alternate sterols that confer protection against self-poisoning by their own saponins. Collectively, these events have enabled sea cucumbers to evolve the ability to produce saponins and saponin-resistant sterols concomitantly.

Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. However, its complex chemical compositions bring certain difficulties to the analysis of this traditional Chinese medicine (TCM). Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR.To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR.The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. Firstly, fragmentation information was obtained in the positive and negative ion modes. Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature.A total of 45 chemical constituents were successfully screened out, including 22 flavonoids, 13 saponins, and 10 amino acids.The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR.

Panax notoginseng is one of the traditional precious and bulk-traded medicinal materials in China. Its anticoagulant activity is related to its saponin composition. However, the correlation between saponins and anticoagulant activities in P. notoginseng from different origins and identification of the origins have been rarely reported.We aimed to analyze the correlation of components and activities of P. notoginseng from different origins and develop a rapid P. notoginseng origin identification method.Pharmacological experiments, HPLC, and ATR-FTIR spectroscopy (variable selection) combined with chemometrics methods of P. notoginseng main roots from four different origins (359 individuals) in Yunnan Province were conducted.The pharmacological experiments and HPLC showed that the saponin content of P. notoginseng main roots was not significantly different. It was the highest in main roots from Wenshan Prefecture (9.86%). The coagulation time was prolonged to observe the strongest effect (4.99 s), and the anticoagulant activity was positively correlated with the contents of the three saponins. The content of ginsenoside RgThis method is a powerful analytical tool for the activity analysis and identification of Chinese medicinal materials from different origins.

Plants often protect themselves from their own bioactive defense metabolites by storing them in less active forms. Consequently, plants also need systems allowing correct spatiotemporal reactivation of such metabolites, for instance under pathogen or herbivore attack. Via co-expression analysis with public transcriptomes, we determined that the model legume Medicago truncatula has evolved a two-component system composed of a β-glucosidase, denominated G1, and triterpene saponins, which are physically separated from each other in intact cells. G1 expression is root-specific, stress-inducible, and coregulated with that of the genes encoding the triterpene saponin biosynthetic enzymes. However, the G1 protein is stored in the nucleolus and is released and united with its typically vacuolar-stored substrates only upon tissue damage, partly mediated by the surfactant action of the saponins themselves. Subsequently, enzymatic removal of carbohydrate groups from the saponins creates a pool of metabolites with an increased broad-spectrum antimicrobial activity. The evolution of this defense system benefited from both the intrinsic condensation abilities of the enzyme and the bioactivity properties of its substrates. We dub this two-component system the saponin bomb, in analogy with the mustard oil and cyanide bombs, commonly used to describe the renowned β-glucosidase-dependent defense systems for glucosinolates and cyanogenic glucosides.

Target-protein-based pesticide screening has attracted wide-ranging attention on pesticide science. Pedunsaponin A (PA) is a compound isolated from the root of Pueraria peduncularis, and it has a strong toxic effect on Pomacea canaliculata. Previous studies found that Advlin (PcAdv) and neural Wiskott-Aldrich syndrome isoform X1(PcnWAS) are target proteins of PA when interacted with P. canaliculata. In this study, we modeled the two target proteins through I-Tasser and identified the pharmacophore of PA binding to the two target proteins by molecular docking. Furthermore, through virtual screening, potassium alginate was found to strongly bind to the target proteins in theory. In vivo bioassay showed that, similar to PA treatment, potassium alginate was able to induce typical poisoning symptoms on P. canaliculata, which were characterized by abnormal increase of excreta, weakening of climbing capacity, loss of gill cilia and decrease in hemocyanin content, and even cause death of P. canaliculata with a 13.33% mortality rate under 100 mg L

Agaves are mainly used to produce alcoholic beverages such as tequila, mezcal and bacanora. However, the leaves constitute more than 50% of the plant and are not used in the production process, so they are considered waste. This plant material can be used as a source of bioactive compounds such as terpenes, flavonoids and saponins. Therefore, the objective of this study was to characterize the aglycone type of saponins and to quantify three steroidal sapogenins in leaves of five Agave species collected in different regions of Guerrero and Oaxaca, Mexico.Analysis by gas chromatography-flame ionization detection of the hydrolyzed methanolic extracts showed that diosgenin and tigogenin were the most abundant sapogenins identified in the five Agave species. Differences in the content of these sapogenins were found in the same species collected in different localities. The leaves of Agave americana var. oaxacensis L. (Oaxaca) had the highest diosgenin-derived saponin content, while the leaves of A. angustifolia Haw. (Guerrero) had the highest tigogenin-derived saponin content. Only in A. cupreata was sarsasapogenin identified, all three sapogenins occurring in the leaves of this species. For the first time, information is provided on the aglycones of the saponins produced in A. potatorum Zucc. and A. karwinskii Zucc.This study made it possible to compare the content of diosgenin and tigogenin-derived saponins in leaves of Agave species from Guerrero and Oaxaca. This information will be useful for better utilization of this plant material and add value to the process of mezcal elaboration. © 2022 Society of Chemical Industry.

As a highly efficient anticancer agent, doxorubicin (DOX) is used for treatment of various cancers, but DOX-induced oxidative damages contribute to a degenerative irreversible cardiac toxicity. Saikosaponin D (SSD), which is a triterpenoid saponin with many biological activities including anti-inflammatory effects and antioxidant properties, provides protection against pathologic cardiac remodeling and fibrosis. In the present study, we investigated the work of SSD for DOX-induced cardiotoxicity and the involved mechanisms. We observed that DOX injection induced cardiac injury and malfunction and decreased survival rate. Besides, DOX treatment increased lactate dehydrogenase leakage, cardiomyocyte apoptosis, and myocardium fibrosis and decreased the size of cardiomyocytes. Meanwhile, all the effects were notably attenuated by SSD treatment. In vitro, we found that 1 μM SSD could enhance the proliferation of H9c2 cells and inhibit DOX-induced apoptosis. It was found that the levels of malondialdehyde (MDA) and reactive oxygen species were significantly reduced by improving the activities of the endogenous antioxidative enzymes including catalase and glutathione peroxidase. Furthermore, SSD treatment could downregulate the DOX-induced p38 phosphorylation. Our results suggested that SSD efficiently protected the cardiomyocytes from DOX-induced cardiotoxicity by inhibiting the excessive oxidative stress via p38-MAPK (mitogen-activated protein kinase, MAPK) signaling pathway.

Astragaloside IV (AS-IV) is an inartificial saponin separated from astragalus membranaceus, which has exhibited key anti-tumor regulation in some cancers. Circular RNAs (circRNAs) are important regulators in malignant development of gastric cancer (GC). Herein, we focused on the molecular mechanism of AS-IV with circRNA dihydrolipoamide S-succinyltransferase (circDLST) in GC. CircDLST, microRNA-489-3p (miR-489-3p), and eukaryotic translation initiation factor 4A1 (EIF4A1) levels were detected by quantitative real-time polymerase-chain reaction and western blot. Cell functions were assessed by cell counting kit-8 assay, ethynyl-2'-deoxyuridine assay, colony formation assay, and transwell assay. The interaction between miR-489-3p and circDLST or EIF4A1 was analyzed by dual-luciferase reporter assay. Xenograft tumor assay was adopted to check the role of circDLST and AS-IV

Hepatotoxicity is a well-known adverse effect of many substances, with toxicity often resulting from interactions of drugs with other drug-like substances. With the increased availability of complementary and alternative medicines, including herbal medicines, the likelihood of adverse interactions between drugs and drug-like substances in herbs increases. However, the impact of potential herb-herb interactions is little understood. To assess the potential of two cytochrome P450 enzyme modulating phytochemicals common to many herbal medicines, atractylenolide I (ATR-I) and astragaloside IV (AST-IV), to interact with coumarin, another phytochemical common in many foods, a hepatocyte function model with a liver carcinoma cell line, HepG2, was exposed to these agents. To determine the effects of cytochrome P450 modulation by these phytochemicals certain cells were induced with rifampicin to induce cytochrome P450. Increasing concentrations of ATR-I combined with a fixed, nontoxic concentration of coumarin (200 µM), demonstrated significant additive interactions. 300 µM ATR-I produced a 31% reduction in cell viability (

The present study was initiated to examine the anticancer effects of Anhuienoside C (AC) against ovarian cancer and postulates the possible molecular mechanism of its action. 3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay was implemented for determination of the effects of AC on cell viability of the ovarian cancer OVACAR-3 cell line. To study cellular morphology, phase contrast microscopy was performed. Apoptosis was examined via acridine orange/ethidium bromide used staining assays. Flow cytometry was used to check the different phases of the cell cycle. Cell migration and invasion assays were performed via transwell chamber assay. The effects of AC on expression of phosphoinositide 3-kinases (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) protein in ovarian cell were assessed using western blotting assay. The results indicated that the cell proliferation rate lowered in AC-treated OVACAR-3 cells as compared to the untreated controls in a dose-dependent manner. Cell morphology changed substantially by the exposure to AC and remained dose dependent. These morphological changes were indicative of apoptotic cell death. Apoptosis analysis showed dose-dependent increase of apoptosis. The cell migration and invasion of OVACAR-3 cells was reduced to a minimum by AC in a dose-dependent manner. Finally, western blotting assay showed blocking of PI3K/AKT/mTOR signaling pathway with increasing AC doses. Taking all together, AC is a potential ovarian cancer inhibitor. It induces its anti-ovarian cancer effects via induction of apoptosis, delaying cell migration and invasion, and blocking PI3K/AKT/mTOR signaling pathway.

The methanol extract from the leaves of Ilex paraguariensis A. St.-Hil. (Aquifoliaceae), popularly known as mate, maté, or yerba maté, inhibits the intracellular triglyceride accumulation in HepG2 cells and suppresses the plasma triglyceride elevation in olive oil-treated mice. Three new triterpene saponins, termed mateosides I (1), II (2), and III (3), were isolated from the extract along with 29 known compounds. The structures of 1-3 were elucidated based on chemical and spectroscopic evidence. Among the isolates, principal saponin constituents, 2 and matesaponins 1 (7) and 2 (9), potently inhibited the triglyceride accumulation in HepG2 cells simultaneously treated with oleic acid and high glucose. In vivo assay of the methanol extract of I. paraguariensis revealed that 7 and 9 showed anti-hyperlipidemic activities in olive oil-treated mice. These results suggested that the saponin constituents of I. paraguariensis could be valuable bioactive marker for the anti-obesogenic activity.

In the conditions of the forest-steppe zone of Western Siberia, a comparative study of the content of secondary metabolites, such as pectins, protopectins, catechins, flavonols, sugars, starch, saponins, ascorbic acid in the vegetative organs of Hemerocallis hybrida of the Bambery Crismas variety, was conducted for the first time. Comparative results of the quantitative composition of spare and biologically active substances in leaves and rhizomes during the three growing seasons of 2017–2019 were obtained. The dynamics of accumulation of these substances relative to the phenological phases of plant development of the Bambery Crismas variety is established. It is shown that the highest concentrations of pectin in rhizomes are observed in all years of the study in July during the flowering period (5.26–8.66%). In the leaves, high pectin readings were observed in different phenophases of plant development: in 2017 during the growing season (0.95%), in 2018 during the flowering period (1.59%), in 2019 during the fruiting period (1.27%). The maximum value of flavonols in the leaves (2.2%) during the fruiting period of plants was revealed. The content of saponins in the leaves corresponded to 12.96-32.81%, in the rhizomes 7.79–53.26% in different years of seasonal development and phenophase. The concentration of catechins in leaves is 2–10 times greater than in rhizomes. A high content of ascorbic acid in the leaves (104.7–120.2 mg%) was found. It was noted that the accumulation of starch in the underground organs of plants increased by 1.5 times in the pre-winter period compared to the spring-summer period and amounted to 27.8–48.4%. The analysis showed that the sugar content in the leaves differed depending on the growing season, but it was 2-8 times higher compared to the leaves. Indications of secondary metabolites in the organs of Bambery Crismas differ in specificity, depend on the growing seasons and phenological phases of the development of plants of this variety., В условиях лесостепной зоны Западной Сибири впервые проведено сравнительное исследование содержания вторичных метаболитов, таких как пектины, протопектины, катехины, флавонолы, сахара, крахмал, сапонины, аскорбиновая кислота в вегетативных органах Hemerocallis hybrida сорта Bambery Crismas. Получены сравнительные результаты количественного состава запасных и биологически активных веществ в листьях и корневищах в течение трех вегетационных периодов 2017–2019 гг. Установлена динамика накопления данных веществ относительно фенологических фаз развития растений сорта Bambery Crismas. Показано, что наибольшие концентрации пектина в корневищах наблюдаются во все годы исследования в июле в период цветения (5.26–8.66%). В листьях высокие показания пектина отмечены в разные фенофазы развития растений: в 2017 г. в период вегетации (0.95%), в 2018 г. в период цветения (1.59%), в 2019 г. в период плодоношения (1,27%). Выявлено максимальное значение флавонолов в листьях (2.2%) в период плодоношения растений. Содержание сапонинов в листьях соответствовало 12.96–32.81%, в корневищах 7.79–53.26% в разные годы сезонного развития и фенофазы. Концентрация катехинов в листьях в 2–10 раз больше, чем в корневищах. Установлено высокое содержание аскорбиновой кислоты в листьях (104.7–120.2 мг%). Отмечено, что накопление крахмала в подземных органах растений увеличивалось к предзимью в 1,5 раза по сравнению с весенне-летним периодом и составляло 27.8–48.4%. Анализ показал, что содержание сахаров в листьях отличалось в зависимости от года вегетации, но его в 2–8 раз больше по сравнению с корневищами. Показания вторичных метаболитов ворганах Bambery Crismas отличаются специфичностью, зависят от вегетационных периодов и фенологических фаз развития растений данного сорта.

Terpenes are one of the most abundant classes of secondary metabolites produced by plants and can be divided based on the number of isoprene units (C

Bacopa monnieri (L.) Wettst. or water hyssop commonly known as "Brahmi" is a small, creeping, succulent herb from the Plantaginaceae family. It is popularly employed in Ayurvedic medicine as a nerve tonic to improve memory and cognition. Of late, this plant has been reported extensively for its pharmacologically active phyto-constituents. The main phytochemicals are brahmine, alkaloids, herpestine, and saponins. The saponins include bacoside A, bacoside B, and betulic acid. Investigation into the pharmacological effect of this plant has thrived lately, encouraging its neuroprotective and memory supporting capacity among others. Besides, it possesses many other therapeutic activities like antimicrobial, antioxidant, anti-inflammatory, gastroprotective properties, etc. Because of its multipurpose therapeutic potential, it is overexploited owing to the prioritization of natural remedies over conventional ones, which compels us to conserve them. B. monnieri is confronting the danger of extinction from its natural habitat as it is a major cultivated medico-botanical and seed propagation is restricted due to less seed availability and viability. The ever-increasing demand for the plant can be dealt with mass propagation through plant tissue culture strategy. Micropropagation utilizing axillary meristems as well as de novo organogenesis have been widely investigated in this plant which has also been explored for its conservation and production of different types of secondary metabolites. Diverse in vitro methods such as organogenesis, cell suspension, and callus cultures have been accounted for with the aim of production and/or enhancement of bacosides. Direct shoot-organogenesis was initiated in excised leaf and internodal explants without any exogenous plant growth regulator(s) (PGRs), and the induction rate was improved when exogenous cytokinins and other supplements were used. Moreover, biotechnological toolkits like Agrobacterium-mediated transformation and the use of mutagens have been reported. Besides, the molecular marker-based studies demonstrated the clonal fidelity among the natural and in vitro generated plantlets also elucidating the inherent diversity among the natural populations. Agrobacterium-mediated transformation system was mostly employed to optimize bacoside biosynthesis and heterologous expression of other genes. The present review aims at depicting the recent research outcomes of in vitro studies performed on B. monnieri which include root and shoot organogenesis, callus induction, somatic embryogenesis, production of secondary metabolites by in vitro propagation, acclimatization of the in vitro raised plantlets, genetic transformation, and molecular marker-based studies of clonal fidelity. KEY POINTS: • Critical and up to date records on in vitro propagation of Bacopa monnieri • In vitro propagation and elicitation of secondary metabolites from B. monnieri • Molecular markers and transgenic studies in B. monnieri.

BACKGROUND: Endogenous pancreatic β-cell regeneration is a promising therapeutic approach for enhancing β-cell function and neogenesis in diabetes. Various findings have reported that regeneration might occur via stimulating β-cell proliferation, neogenesis, or conversion from other pancreatic cells to β-like cells. Although the current scenario illustrates numerous therapeutic strategies and approaches that concern endogenous β-cell regeneration, all of them have not been successful to a greater extent because of cost effectiveness, availability of suitable donors and rejection in case of transplantation, or lack of scientific evidence for many phytochemicals derived from plants that have been employed in traditional medicine. Therefore, the present study aims to investigate the effect of gymnemic acid (GA) on β-cell regeneration in streptozotocin-induced type 1 diabetic rats and high glucose exposed RIN5-F cells. METHODS: The study involves histopathological and immunohistochemical analysis to examine the islet’s architecture. Quantitative polymerase chain reaction (qPCR) and/or immunoblot were employed to quantify the β-cell regeneration markers and cell cycle proliferative markers. RESULTS: The immunoexpression of E-cadherin, β-catenin, and phosphoinositide 3-kinases/protein kinase B were significantly increased in GA-treated diabetic rats. On the other hand, treatment with GA upregulated the pancreatic regenerative transcription factor viz. pancreatic duodenal homeobox 1, Neurogenin 3, MafA, NeuroD1, and β-cells proliferative markers such as CDK4, and Cyclin D1, with a simultaneous downregulation of the forkhead box O, glycogen synthase kinase-3, and p21(cip1) in diabetic treated rats. Adding to this, we noticed increased nuclear localization of Pdx1 in GA treated high glucose exposed RIN5-F cells. CONCLUSION: Our results suggested that GA acts as a potential therapeutic candidate for endogenous β-cell regeneration in treating type 1 diabetes. GRAPHICAL ABSTRACT: [Image: see text]

Chikusetsusaponin IV and V (CsIV and CsV), two typical oleanolic acid saponins, are mainly derived from the rhizome of Panax japonicus C.A. Mey. To reveal the anti-cancer effect of CsIV and CsV on liver cancer cells, human hepatic cancer cell lines (HepG2) were exposed to these saponins, and various physiological responses of HepG2 were investigated.HepG2 cells were treated with CsIV, CsV and 5-fluorouracil (5-FU). Cell proliferation was measured by CCK-8 assay. The cell cycle arrest, cell apoptosis and intracellular CaOur data demonstrated that CsIV and CsV exerted significant cytotoxic effects on HepG2 cells without affecting normal liver cells. And, these chikusetsusaponins, especially for CsIV, showed a potent effect on promoting cell apoptosis in HepG2 cells, which was associated with the activation of p53-mediated apoptosis pathway.

Targeting the PPARγ might be a potential therapeutic strategy for diabetes-associated cognitive decline (DACD). In this study, Gypenoside LXXV (GP-75), a dammarane-type triterpene compound isolated from Gynostemma pentaphyllum, was found to be a novel PPARγ agonist using a dual-luciferase reporter assay system. However, whether GP-75 has protective effects against DACD remains unknown. Interestingly, intragastric administration of GP-75 (40 mg/kg/day) for 12 weeks significantly attenuated the cognitive deficit in db/db mice. GP-75 treatment significantly improved the glucose tolerance and lipid metabolism, and suppressed neuroinflammation. Notably, GP-75 treatment dramatically increased the uptake of glucose by the brain, as detected by

The interactions between Chinese herbs and drugs pose a great challenge to the combined clinical application of Chinese herbs and drugs. Chinese medicinal products contain complex pharmacologically active components that may influence the in vivo processes of drugs in a variety of ways. In China, drugs based on Panax ginseng total saponins (PNS) are often combined with warfarin for the treatment of cardiovascular diseases.To assess the effects of Panax notoginseng saponins (PNS) on the pharmacokinetics of warfarin and its mechanism.Blood was collected for the determination of the prothrombin time (PT) and international normalized ratio (INR) from rats treated with warfarin alone or with warfarin + PNS. The plasma concentration of warfarin was determined by high-performance liquid chromatography. Western blot was used to detect the expression of cytochrome P450 (CYP) enzymes.When warfarin and PNS were co-administered, the PT and INR increased compared to when warfarin was given alone. 72 hours after administration, compared to the warfarin alone group, the warfarin + low-dose PNS, warfarin + medium-dose PNS, and warfarin + high-dose PNS groups showed 110%, 122%, and 126% increases in PT, respectively (all P0.05), as well as 111%, 124%, and 128% increases in INR (all P0.05). Compared with the warfarin alone group, the clearance rate (CL/F) of warfarin in the warfarin + low-dose PNS, warfarin + medium-dose PNS, and warfarin + high-dose PNS groups was 10% (P 0.05), 23% (P 0.05), and 33% (P 0.05) lower, respectively, while the systemic exposure (area under the concentration-time curve, AUCPNS can increase the blood concentration of warfarin, as well as the exposure time, and it can enhance the anticoagulant effect of warfarin by inhibiting the expression of the liver enzyme CYP3A4.

Activation of the NLRP3 inflammasome and its mediated neuroinflammation are implicated in neurodegenerative diseases, while mitophagy negatively regulates NLRP3 inflammasome activation. SHP-2, a protein-tyrosine phosphatase, is critical for NLRP3 inflammasome regulation and inflammatory responses. In this study, we investigated whether triterpenoid saponins in Radix Polygalae inhibit the NLRP3 inflammasome via mitophagy induction. First, we isolated the active fraction (polygala saponins (PSS)) and identified 17 saponins by ultra-performance liquid chromatography coupled with diode-array detection and tandem quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q/TOF-MS). In microglial BV-2 cells, PSS induced mitophagy as evidenced by increased co-localization of LC3 and mitochondria, as well as an increased number of autophagic vacuoles surrounding the mitochondria. Furthermore, the mechanistic study found that PSS activated the AMPK/mTOR and PINK1/parkin signaling pathways via the upregulation of SHP-2. In Aβ(1-42)-, A53T-α-synuclein-, or Q74-induced BV-2 cells, PSS significantly inhibited NLRP3 inflammasome activation, which was attenuated by bafilomycin A1 (an autophagy inhibitor) and SHP099 (an SHP-2 inhibitor). In addition, the co-localization of LC3 and ASC revealed that PSS promoted the autophagic degradation of the NLRP3 inflammasome. Moreover, PSS decreased apoptosis in conditioned medium-induced PC-12 cells. In APP/PS1 mice, PSS improved cognitive function, ameliorated Aβ pathology, and inhibited neuronal death. Collectively, the present study, for the first time, shows that PSS inhibit the NLRP3 inflammasome via SHP-2-mediated mitophagy in vitro and in vivo, which strongly suggests the therapeutic potential of PSS in various neurodegenerative diseases.

Osteoarthritis (OA), an inflammatory response in chondrocytes, leads to extracellular matrix (ECM) degradation and cartilage destruction. Timosaponin B-II (TB-II) is the main bioactive component of Rhizoma Anemarrhenae with reported antioxidant and anti-inflammatory effects. This study investigated the anti-OA function and mechanism of TB-II on IL-1β-stimulated SW1353 cells and primary rat chondrocytes. We firstly screened the concentration of TB-II in SW1353 cells and primary rat chondrocytes using CCK-8 assay. Thereafter, SW1353 cells and chondrocytes were, respectively, pretreated with TB-II (20 and 40 μg/mL) and TB-II (10 and 30 μg/mL) for 24 h and then stimulated with interleukin 1β (IL-1β, 10 ng/mL) for another 24 hours. Results showed that TB-II suppressed the production of reactive oxygen species, the protein levels of inducible nitric oxide synthase and cyclooxygenase-2 in IL-1β-stimulated SW1353 cells and chondrocytes. IL-1β-induced high secretion levels of nitric oxide and prostaglandin 2, TNF-α, IL-6 and MCP-1 were down-regulated by TB-II treatment, indicating an anti-inflammatory effect of TB-II on OA in vitro condition. Moreover, TB-II weakened the mRNA and protein expression of (matrix metalloproteinase) MMPs including MMP-1, MMP-3, and MMP-13, indicating the protection of TB-II against ECM degradation. Mechanically, TB-II suppressed MAPKs and NF-κB pathways under IL-1β stimulation evidenced by the down-regulated protein expression of p-ERK, p-p38, p-JNK, p-p65 and the reduced translocation of p65 subunit to the nucleus. The present study demonstrated that TB-II might become a novel therapeutic agent for OA treatment through repressing IL-1β-stimulated inflammation, oxidative stress and ECM degradation via suppressing the MAPKs and NF-κB pathways.

Phoenix dactylifera fruits, commonly known as date fruits are consumed worldwide because of their nutritional and pharmacological values owing to their nutrients and phytoconstituents compositions. This study was undertaken to evaluate and compare anti-inflammatory and analgesic activities of methanol and n-hexane extracts of P. dactylifera fruits in Wistar rats. Egg albumin and carrageenan-induced inflammation models were used to evaluate the anti-inflammatory activities, while acetic acid and formalin-induced pain models were used to evaluate the analgesic activities in Wistar rats. Each model comprised of eight groups of three rats each. Groups administered with 300 mg/kg bw and 600 mg/kg bw of the n-hexane and methanol extracts, respectively exhibited maximum percentage inhibition. The maximum percentage inhibitions of methanol extract on egg albumin and carrageenan, acetic acid and formalin-induced pain at 600 mg/kg bw. (67.24% and 64.22%, 63.33% and 65.32%, respectively) were significantly higher (p < 0.05) than that of the n-hexane extract at 300 mg/kg bw. (56.90% and 52.94%, 50.00% and 52.56%, respectively). Conclusively, both extracts possess anti-inflammatory and analgesic activities, with methanol extract showing greater activity. These activities may be due to the presence of tannins, saponins, but most especially flavonoids in both extracts.

Vaccination is one of the basic strategies in the fight against foot-and-mouth disease (FMD) in endemic regions. Today, commercially available FMD vaccines are prepared with inactive whole virion, which has low immunogenicity. Therefore, considerable effort has been devoted to finding novel adjuvants. Although mineral oils are among the most common adjuvants, it is still difficult to provide a long-term and robust immune response. Combined adjuvant systems are currently being studied to solve the problem. Saponins and CpG-ODNs have been shown to increase the immune response to vaccines individually in various studies. In this study, the effect of different adjuvants and their combinations (Quil-A, E. coli DNA, and MontanideTM ISA 206) on total and neutralizing antibody response in sheep was investigated. According to the results, the Quil-A group induced the highest antibody level, followed by the combination of Quil-A and the E. coli DNA group. The group containing E. coli DNA also caused a higher antibody response than the group containing only MontanideTM ISA 206 for certain days of sampling. These affordable alternatives of saponin and CpG sources can be used individually to increase the potency of the FMD vaccine for mass vaccinations of sheep. Keywords: foot-and-mouth disease; vaccine; adjuvant; Quil-A; E. coli DNA; combination of adjuvants.

Platycodin D is a major constituent in the root of Platycodon grandiflorum and has diverse pharmacologic activities, including anti-inflammatory, anti-allergic, and antitumor activities. Vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are potent angiogenic factors and contribute to tumor angiogenesis by directly and indirectly promoting angiogenic processes, including the proliferation, adhesion, migration, and tube formation of endothelial cells. Here, we found that platycodin D at noncytotoxic concentrations inhibited VEGF-induced proliferation, adhesion to the extracellular matrix proteins fibronectin and vitronectin, chemotactic motility, and tube formation of human umbilical vein endothelial cells (HUVECs). Platycodin D reduced the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) and the secretion of IL-8 in VEGF-stimulated HUVECs. Moreover, platycodin D inhibited tube formation and the phosphorylation of ERK and p38 in IL-8-stimulated HUVECs. The in vitro anti-angiogenic activity of platycodin D was confirmed by in vivo experimental models. Platycodin D inhibited the formation of new blood vessels into mouse Matrigel plugs with VEGF or IL-8. In mice injected with MDA-MB-231 human breast cancer cells, orally administered platycodin D inhibited tumor growth, the number of CD34 [Formula: see text]vessels, and the expression of VEGF and IL-8. Taken together, platycodin D directly and indirectly prevents VEGF-induced and IL-8-induced angiogenesis by blocking the activation of mitogen-activated protein kinases (MAPKs). Platycodin D may be beneficial for the prevention or treatment of tumor angiogenesis and angiogenesis-related human diseases.

Spontaneous intracerebral hemorrhage (ICH) is associated with high mortality and disability rates. The microglia-induced inflammatory response is a critical factor determining brain tissue damage after ICH. Raddeanin A (RA) is a natural triterpenoid compound with anti-inflammatory effects, although its effects on ICH and the underlying molecular mechanism have not been elucidated. In this study, we found that RA reduced the volume of cerebral hematoma and cerebral edema, attenuated neuronal apoptosis and improved the behavioral indices in a murine model of acute cerebral hemorrhage. Mechanistically, RA downregulated the TLR4-mediated pro-inflammatory effectors, reduced infiltration of microglia in peri-intracerebral hemorrhage and inhibited apoptosis of neurons co-cultured with activated microglia. In conclusion, RA can alleviate ICH-related tissue damage and promote the recovery of neuronal function by suppressing microglia-induced inflammation and apoptosis.

There is currently a lack of scientific understanding regarding how bio-surfactants influence the mobility of graphene oxide (GO) through saturated porous media. In this study, the transport characteristics of GO through porous media with different heterogeneities (

At present, the evaluation methods for pharmaceutical properties of Chinese medicinal films have many problems, such as poor objectivity for the indexes and no quantitative and standardized evaluation methods. This study established a new method using three important physical property parameters, i.e., flow index, weight loss rate, and elongation rate, which were closely related to the pharmaceutical properties of films. On this basis, the above parameters were taken as indicators to optimize the film formulation of Trillium tschonoskii total saponins and verify the feasibility and suitability of the established method and parameters in formulation optimization. A self-made flow distance detection device and a viscometer were used to measure and characterize the fluidity, where the flow index refers to the ratio of the flow distance per unit time to the viscosity. The weight loss rate was measured by the 3 M transpore~(TM) surgical tape. The film-forming property was characterized by the weight loss rate of the sample within a certain period of time. An electronic tension machine was employed to measure the elongation rate after drying, which was used to characterize the ductility of the film. The results showed that the established method for the determination of flow index, weight loss rate, and elongation rate was stable and reliable. The optimal film formulation of T. tschonoskii total saponins could be obtained by optimization with those indicators. As demonstrated, the above evaluation indicators(flow index, weight loss rate, and elongation rate) can guide the optimization and design of formulation, and the new evaluation method constructed based on this shows a good application prospect in formulation optimization and formulation quality evaluation of medicinal films.