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1.
J Cell Mol Med ; 28(6): e18146, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38426932

RESUMO

Acne vulgaris represents a chronic inflammatory condition, the pathogenesis of which is closely associated with the altered skin microbiome. Recent studies have implicated a profound role of Gram-negative bacteria in acne development, but there is a lack of antiacne agents targeting these bacteria. Polyphyllins are major components of Rhizoma Paridis with great anti-inflammatory potential. In this study, we aimed to evaluate the antiacne effects and the underlying mechanisms of PPH and a PPH-enriched Rhizoma Paridis extract (RPE) in treating the Gram-negative bacteria-induced acne. PPH and RPE treatments significantly suppressed the mRNA and protein expressions of interleukin (IL)-1ß and IL-6 in lipopolysaccharide (LPS)-induced RAW 264.7 and HaCaT cells, along with the intracellular reactive oxygen species (ROS) generation. Furthermore, PPH and RPE inhibited the nuclear translocation of nuclear factor kappa-B (NF-κB) P65 in LPS-induced RAW 264.7 cells. Based on molecular docking, PPH could bind to kelch-like ECH-associated protein 1 (KEAP1) protein. PPH and RPE treatments could activate nuclear factor erythroid 2-related factor 2 (NRF2) and upregulate haem oxygenase-1 (HO-1). Moreover, RPE suppressed the mitogen-activated protein kinase (MAPK) pathway. Therefore, PPH-enriched RPE showed anti-inflammatory and antioxidative effects in vitro, which is promising for alternative antiacne therapeutic.


Assuntos
Acne Vulgar , Saponinas , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lipopolissacarídeos/efeitos adversos , Saponinas/farmacologia , Saponinas/uso terapêutico , Simulação de Acoplamento Molecular , Anti-Inflamatórios/uso terapêutico , NF-kappa B/metabolismo , Bactérias Gram-Negativas/metabolismo , Acne Vulgar/tratamento farmacológico , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Inflamação/metabolismo
2.
BMC Plant Biol ; 24(1): 161, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38429697

RESUMO

BACKGROUND: Drought impairs growth, disturbs photosynthesis, and induces senescence in plants, which results in crop productivity reduction and ultimately jeopardizes human food security. The objective of this study was to determine major parameters associated with drought tolerance and recovery ability of fenugreek (Trigonella foenum-graecum L.), by examining differential biochemical and phenological responses and underlying enzyme activities as well as melatonin roles during drought stress and re-watering for two contrasting landraces. Moreover, the relative expression of three key genes involved in the biosynthesis pathway of diosgenin, including SQS, CAS, and BG, was investigated. RESULTS: Depending on the conditions, drought stress enhanced the activity of antioxidant enzymes and the osmoregulating compounds, non-enzymatic antioxidants, hydrogen peroxide content, and lipid peroxidation levels in most cases. Severe drought stress accelerated flowering time in Shushtar landrace (SHR) but had no significant effects on Varamin (VR). Pretreatment with melatonin delayed flowering time in SHR and caused high drought resistance in this landrace. Furthermore, melatonin significantly enhanced drought adaptability in VR by improving plant recovery ability. DISCUSSION: Based on our results plants' responses to drought stress and melatonin pretreatment were completely landrace-specific. Drought stress caused an increase in the relative expression of CAS gene and ultimately the accumulation of steroidal saponins in SHR. Melatonin compensated for the decrease in biomass production due to drought stress and finally increased steroidal saponins performance in SHR. Our study showed that melatonin can improve drought stress and recovery in fenugreek, but different factors such as genotype, melatonin concentration, and plant age should be considered.


Assuntos
Melatonina , Saponinas , Trigonella , Humanos , Melatonina/metabolismo , Trigonella/genética , Trigonella/metabolismo , Secas , Antioxidantes/metabolismo
3.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474161

RESUMO

Obesity is a serious global health challenge, closely associated with numerous chronic conditions including type 2 diabetes. Anemarrhena asphodeloides Bunge (AA) known as Jimo has been used to address conditions associated with pathogenic heat such as wasting-thirst in Korean Medicine. Timosaponin A3 (TA3), a natural compound extracted from AA, has demonstrated potential therapeutic effects in various disease models. However, its effects on diabetes and obesity remain largely unexplored. We investigated the anti-obesity and anti-diabetic properties of TA3 using in vitro and in vivo models. TA3 treatment in NCI-H716 cells stimulated the secretion of glucagon-like peptide 1 (GLP-1) through the activation of phosphorylation of protein kinase A catalytic subunit (PKAc) and 5'-AMP-activated protein kinase (AMPK). In 3T3-L1 adipocytes, TA3 effectively inhibited lipid accumulation by regulating adipogenesis and lipogenesis. In a high-fat diet (HFD)-induced mice model, TA3 administration significantly reduced body weight gain and food intake. Furthermore, TA3 improved glucose tolerance, lipid profiles, and mitigated hepatic steatosis in HFD-fed mice. Histological analysis revealed that TA3 reduced the size of white adipocytes and inhibited adipose tissue generation. Notably, TA3 downregulated the expression of lipogenic factor, including fatty-acid synthase (FAS) and sterol regulatory element-binding protein 1c (SREBP1c), emphasizing its potential as an anti-obesity agent. These findings revealed that TA3 may be efficiently used as a natural compound for tackling obesity, diabetes, and associated metabolic disorders, providing a novel approach for therapeutic intervention.


Assuntos
Fármacos Antiobesidade , Diabetes Mellitus Tipo 2 , Saponinas , Animais , Camundongos , Obesidade/metabolismo , Esteroides/farmacologia , Fármacos Antiobesidade/farmacologia , Adipogenia , Proteínas Quinases Ativadas por AMP/metabolismo , Lipídeos/farmacologia , Células 3T3-L1 , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL
4.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474179

RESUMO

Ischemic stroke is associated with a high mortality rate, and effective treatment strategies are currently lacking. In this study, we aimed to develop a novel nano delivery system to treat ischemic stroke via intranasal administration. A three-factor Box-Behnken experimental design was used to optimize the formulation of liposomes co-loaded with Panax notoginseng saponins (PNSs) and Ginsenoside Rg3 (Rg3) (Lip-Rg3/PNS). Macrophage membranes were coated onto the surface of the optimized liposomes to target the ischemic site of the brain. The double-loaded liposomes disguised by macrophage membranes (MM-Lip-Rg3/PNS) were spherical, in a "shell-core" structure, with encapsulation rates of 81.41% (PNS) and 93.81% (Rg3), and showed good stability. In vitro, MM-Lip-Rg3/PNS was taken up by brain endothelial cells via the clathrin-dependent endocytosis and micropinocytosis pathways. Network pharmacology experiments predicted that MM-Lip-Rg3/PNS could regulate multiple signaling pathways and treat ischemic stroke by reducing apoptosis and inflammatory responses. After 14 days of treatment with MM-Lip-Rg3/PNS, the survival rate, weight, and neurological score of middle cerebral artery occlusion (MCAO) rats significantly improved. The hematoxylin and eosin (H&E) and TUNEL staining results showed that MM-Lip-Rg3/PNS can reduce neuronal apoptosis and inflammatory cell infiltration and protect the ischemic brain. In vivo biological experiments have shown that free Rg3, PNS, and MM-Lip-Rg3/PNS can alleviate inflammation and apoptosis, especially MM-Lip-Rg3/PNS, indicating that biomimetic liposomes can improve the therapeutic effects of drugs. Overall, MM-Lip-Rg3/PNS is a potential biomimetic nano targeted formulation for ischemic stroke therapy.


Assuntos
AVC Isquêmico , Saponinas , Ratos , Animais , Lipossomos/química , Células Endoteliais , Administração Intranasal , Saponinas/farmacologia , Macrófagos
5.
Cell Mol Biol (Noisy-le-grand) ; 70(2): 128-136, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38430031

RESUMO

As the main active ingredient of Astragalus, Astragaloside IV (AS-IV) can ameliorate pulmonary fibrosis. In this experiment, we studied how AS-IV reduces idiopathic pulmonary fibrosis (IPF). Bleomycin (BLM) or TGF-ß1 was treated in mice or alveolar epithelial cells to mimic IPF in vivo as well as in vitro. ASV-IV alleviated levels of inflammatory cytokines and fibrosis markers in IPF model. Through detection of autophagy-related genes, ASV-IV was observed to induce autophagy in IPF. Besides, ASV-IV inhibited miR-21 expression in IPF models, and overexpression of miR-21 could reverse the protective potential of ASV-IV on IPF. PTEN was targeted by miR-21 and was up-regulated by ASV-IV in IPF models. In addition, levels of inflammatory cytokines and fibrosis markers, autophagy, as well as the PI3K/AKT/mTOR pathway regulated by ASV-IV could be neutralized after treatment with autophagy inhibitors, miR-21 mimics, or si-PTEN. Our study demonstrates that ASV-IV inhibits IPF through activation of autophagy by miR-21-mediated PTEN/PI3K/AKT/mTOR pathway, suggesting that ASV-IV could be acted to be a promising therapeutic method for IPF.


Assuntos
Fibrose Pulmonar Idiopática , MicroRNAs , Saponinas , Triterpenos , Animais , Camundongos , Autofagia/efeitos dos fármacos , Fibrose , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/farmacologia , Saponinas/uso terapêutico , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Triterpenos/farmacologia , Triterpenos/uso terapêutico , PTEN Fosfo-Hidrolase/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo
6.
Chem Biol Drug Des ; 103(3): e14481, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38458969

RESUMO

Studies have shown that saikosaponin D (SSD) has favorable neurotherapeutic effects. Therefore, the objective of this study was to explore the efficacy and possible molecular mechanisms of SSD on pilocarpine (PP)-induced astrocyte injury. Primary astrocytes were isolated from juvenile rats and identified using immunofluorescence. The cells were treated with PP and/or SSD for 6 h and 12 h, respectively, followed by measurement of their viability through 3-(4,5-dimethylthiazol)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Next, quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of Glial fibrillary acidic protein (GFAP), C3, S100 calcium binding protein A10 (S100a10), pentraxin 3 (Ptx3), toll-like receptor 4 (TLR4), and RAG in astrocytes after different treatments. Enzyme-linked immunosorbent assay and biochemical tests were utilized to evaluate the level of inflammatory factors [interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α)] secreted by cells and the content of oxidative stress-related factors (malondialdehyde [MDA] and glutathione [GSH]) or enzyme activity (catalase [CAT] and glutathione peroxidase [GPX]) in cells. The JC-1 mitochondrial membrane potential (MMP) fluorescence probe was used to measure the MMP in astrocytes. Additionally, western blot was applied to test the expression of proteins related to the nod-like receptor protein 3 (NLRP3)/caspase-1 signaling pathway. PP treatment (1 mM) induced cell injury by significantly reducing the viability of astrocytes and expression of cellular markers. SSD treatment (4 µM) had no toxicity to astrocytes. Besides, SSD (4 µM) treatment could significantly up-regulate the cell viability and marker expression of PP-induced astrocytes. Furthermore, SSD could be employed to inhibit inflammation (reduce IL-1ß, IL-6, and TNF-α levels) and oxidative stress (decrease MDA level, elevate GSH level, the activity of CAT and GPX), and ameliorate mitochondrial dysfunction (upregulate JC-1 ratio) in PP-induced astrocytes. Moreover, further mechanism exploration revealed that SSD treatment significantly reduced the activity of the NLRP3/caspase-1 signaling pathway activated by PP induction. SSD increased cell viability, inhibited inflammation and oxidative stress response, and ameliorated mitochondrial dysfunction in PP-induced astrocyte injury model, thus playing a neuroprotective role. The mechanism of SSD may be related to the inhibition of the NLRP3/caspase-1 inflammasome.


Assuntos
Benzimidazóis , Carbocianinas , Doenças Mitocondriais , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ácido Oleanólico/análogos & derivados , Saponinas , Ratos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Astrócitos/metabolismo , Astrócitos/patologia , Pilocarpina/toxicidade , Fator de Necrose Tumoral alfa/genética , Caspases/metabolismo , Interleucina-6 , Transdução de Sinais , Inflamação/metabolismo
7.
Arch Microbiol ; 206(4): 176, 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38493413

RESUMO

The stems and leaves of Panax notoginseng contain high saponins, but they are often discarded as agricultural waste. In this study, the predominant ginsenosides Rg1, Rc, and Rb2, presented in the stems and leaves of ginseng plants, were biotransformed into value-added rare ginsenosides F1, compound Mc1 (C-Mc1), and Rd2, respectively. A fungal strain YMS6 (Penicillium sp.) was screened from the soil as a biocatalyst with high selectivity for the deglycosylation of major ginsenosides. Under the optimal fermentation conditions, the yields of F1, C-Mc1, and Rd2 were 97.95, 68.64, and 79.58%, respectively. This study provides a new microbial resource for the selective conversion of protopanaxadiol-type and protopanaxatriol-type major saponins into rare ginsenosides via the whole-cell biotransformation and offers a solution for the better utilization of P. notoginseng waste.


Assuntos
Ginsenosídeos , Saponinas , Agricultura , Biotransformação
8.
Chem Biol Drug Des ; 103(3): e14508, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38514749

RESUMO

Pulmonary Fibrosis (PF) is a fatal lung disease with complicated pathogenesis. Astragaloside IV (ASV) has been discovered to alleviate PF progression, and the potential molecular mechanism of ASV in the development of PF need to be further clarified. Bleomycin (BLM) was used to construct PF in vivo model. Expression levels of circ_0008898, miR-211-5p, high mobility group protein B1 (HMGB1), alpha smooth muscle Actin (α-SMA) and Collagen I were examined by Quantitative real time polymerase chain reaction (qRT-PCR) and western blot. Cell survival was analyzed using Cell Counting Kit-8 (CCK-8) and EdU (5-ethynyl-2'-deoxyuridine) assay. The invasion abilities were investigated by transwell assay. The levels of inflammatory factors were tested via using Enzyme-linked immunosorbent assay (ELISA). The relationship between circ_0008898 or HMGB1 and miR-211-5p was identified by dual-luciferase reporter assay. The results showed that ASV attenuated BLM-induced pulmonary fibrosis in vivo. In vitro study, ASV alleviated TGF-ß1-induced fibrogenesis in HFL1 cells. Circ_0008898 was increased in TGF-ß1-induced HFL1 cells. ASV-induced impacts were abrogated by circ_0008898 overexpression in TGF-ß1-induced HFL1 cells. Mechanistically, circ_0008898 competitively bound to miR-211-5p to increase the expression of its target HMGB1. MiR-211-5p deficiency rescued ASV-mediated effects in TGF-ß1-induced HFL1 cells. In addition, HMGB1 overexpression partially overturned circ_0008898 interference-induced impacts in HFL1 cells upon TGF-ß1 treatment. In conclusion, our work manifested that ASV hindered PF process by mediating the circ_0008898/miR-211-5p/HMGB1 network.


Assuntos
Proteína HMGB1 , MicroRNAs , Fibrose Pulmonar , Saponinas , Triterpenos , Humanos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/genética , Fator de Crescimento Transformador beta1/genética , Proteína HMGB1/genética , MicroRNAs/genética , Proliferação de Células
9.
Int Immunopharmacol ; 130: 111749, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38430804

RESUMO

AIMS: Saikosaponin F (SsF) is one of the major active ingredients of Radix Bupleuri, an herb widely used in the treatment of depression. Studies have shown that dry eye disease often occurs together with depression. The aim of this study is to investigate whether SsF can improve depression-associated dry eye disease and explore the underlying mechanism. METHODS: Behavioral test was used to verify the effect of SsF on CUMS-induced depression-like behaviors in mice. Corneal fluorescein staining, phenol red cotton thread test and periodic acid-Schiff (PAS) staining were used to observe the effect of SsF on depression-associated dry eye disease. Western blot (WB) was performed to observe the expression of TAK1 protein and key proteins of NF-κB and MAPK (P38) inflammatory pathways in the hippocampus and cornea. Immunohistochemical staining was used to observe the expression of microglia, and immunoprecipitation was used to observe K63-linked TAK1 ubiquitination. Subsequently, we constructed a viral vector sh-TAK1 to silence TAK1 protein to verify whether SsF exerted its therapeutic effect based on TAK1. The expression of inflammatory factors such as IL-1ß, TNF-α and IL-18 in hippocampus and cornea were detected by ELISA. Overexpression of TRIM8 (OE-TRIM8) by viral vector was used to verify whether SsF improved depression-associated dry eye disease based on TRIM8. RESULTS: SsF treatment significantly improved the depression-like behavior, increased tear production and restored corneal injury in depression-related dry eye model mice. SsF treatment downregulated TAK1 expression and TRIM8-induced K63-linked TAK1 polyubiquitination, while inhibiting the activation of NF-κB and MAPK (P38) inflammatory pathways and microglial expression. In addition, selective inhibition of TAK1 expression ameliorated depression-associated dry eye disease, while overexpression of TRIM8 attenuated the therapeutic effect of SsF on depression-associated dry eye disease. CONCLUSION: SsF inhibited the polyubiquitination of TAK1 by acting on TRIM8, resulting in the downregulation of TAK1 expression, inhibition of inflammatory response, and improvement of CUMS-induced depression-associated dry eye disease.


Assuntos
Síndromes do Olho Seco , NF-kappa B , Ácido Oleanólico/análogos & derivados , Saponinas , Camundongos , Animais , NF-kappa B/metabolismo , Inflamação/metabolismo , Depressão/tratamento farmacológico , Depressão/etiologia , Ubiquitinação , Síndromes do Olho Seco/tratamento farmacológico
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(2): 244-251, 2024 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-38501409

RESUMO

OBJECTIVE: To investigate the protective effect of total saponins of Panax japonicus (TSPJ) against CCl4-induced acute liver injury (ALI) in rats and explore the underlying pharmacological mechanisms. METHODS: Male SD rat models of CCl4-induced ALI were given intraperitoneal injections of distilled water, 100 mg/kg biphenyl bisabololol, or 50, 100, and 200 mg/kg TSPJ during modeling (n=8). Liver functions (AST, ALT, TBil and ALP) of the rats were assessed and liver pathologies were observed with HE staining. Immunohistochemistry was used to detect the expressions of PI3K/Akt/NF-κB signaling pathway molecules in liver tissue; ELISA was used to determine the levels of T-SOD, GSH-Px, and MDA. Western blotting was performed to detect the expression levels of PI3K-Akt and SIRT6-NF-κB pathways in the liver tissue. RESULTS: Network pharmacological analysis indicated that the key pathways including PI3K/Akt mediated the therapeutic effect of TSPJ on ALI. In the rat models of ALI, treatments with biphenyl bisabololol and TSPJ significantly ameliorated CCl4-induced increase of serum levels AST, ALT, ALP, TBil and MDA and decrease of T-SOD and GSH-Px levels (all P < 0.01). The rat models of ALI showed significantly increased expression of p-NF-κB (P < 0.01), decreased expressions of PI3K, p-Akt and SIRT6 proteins, and elevated expression levels of p-NF-κB, TNF-α and IL-6 proteins in the liver, which were all significantly improved in the treatment groups (P < 0.05 or 0.01). CONCLUSION: TSPJ can effectively alleviate CCl4-induced ALI in rats by suppressing inflammatory responses and oxidative stress in the liver via regulating the PI3K/Akt and SIRT6/NF-κB pathways.


Assuntos
Compostos de Bifenilo , Panax , Saponinas , Sirtuínas , Ratos , Masculino , Animais , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Saponinas/farmacologia , Saponinas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Panax/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Fígado/metabolismo , Sirtuínas/metabolismo , Sirtuínas/farmacologia , Superóxido Dismutase/metabolismo
11.
Se Pu ; 42(3): 234-244, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38503700

RESUMO

Ziziphi Spinosae Semen refers to the dried seed of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou. The seed is composed of a reddish brown coat and a yellow kernel. A comparative study was conducted to investigate differences in the chemical composition and their relative contents between the seed coat and kernel of Ziziphi Spinosae Semen. First, the chemical compounds found in the seed coat and kernel were characterized and identified using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The analytical results tentatively identified 57 chemical compounds based on reference-compound comparison, literature retrieval, and chemical-database (e. g., MassBank) searches; these compounds included 14 triterpenes, 23 flavonoids, 7 alkaloids, 6 carboxylic acids, and 7 other types of compounds. The mass error of the identified compounds was within the mass deviation range of 5×10-6 (5 ppm). Next, two methods of multivariate statistical analysis, namely, principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), were used to compare the differential compounds between the two seed parts. A total of 17 differential compounds were screened out via OPLS-DA based on a variable importance in projection (VIP) value of >5. The results revealed that betulinic acid, betulonic acid, alphitolic acid, and jujuboside Ⅰ mainly existed in the seed coat whereas the 13 other compounds, such as spinosin, jujuboside A, and 6‴-feruloylspinosin, mainly existed in the seed kernel. Therefore, these 17 differential compounds can be used to distinguish between the two seed parts. Finally, a semiquantitative method was established using UPLC and a charged aerosol detector (CAD) with inverse gradient compensation in the mobile phase. Six representative compounds with different types were selected to examine the CAD response consistency: magnoflorine (alkaloid), spinosin (flavone), 6‴-feruloylspinosin (flavone), jujuboside A (triterpenoid saponin), jujuboside B (triterpenoid saponin), and betulinic acid (triterpenoid acid). The results showed that the relative standard deviation (RSD) of the average response factors at different levels of these six compounds was 7.04% and that their response intensities were similar. Moreover, each compound in the fingerprint demonstrated good response consistency, and the peak areas obtained directly reflected the contents of each compound. Based on the semiquantitative fingerprints obtained, betulinic acid and oleic acid were considered the main components of the seed coat. The betulinic acid content in the seed coat was approximately 7 times higher than that in the seed kernel. Spinosin, jujuboside A, linoleic acid, betulinic acid, and oleic acid were the main components of the seed kernel. The spinosin content in the seed kernel was 18 times higher than that in the seed coat. In addition, the jujuboside A content in the seed kernel was 24 times higher than that in the seed coat. The proposed method can accurately determine the main components and compare the relative contents of these components in different seed parts. In summary, this study identified the differences in chemical components between the seed coat and kernel of Ziziphi Spinosae Semen and clarified the main components and their relative contents in these parts. The findings can not only provide a basis for the identification of chemical compounds and quality research on different parts of Ziziphi Spinosae Semen but also promote the development and utilization of this traditional Chinese medicine.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Flavonas , Saponinas , Triterpenos , Ziziphus , Medicamentos de Ervas Chinesas/química , Ácido Betulínico , Saponinas/química , Ácidos Oleicos , Cromatografia Líquida de Alta Pressão , Ziziphus/química , Sementes
12.
BMC Plant Biol ; 24(1): 170, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443797

RESUMO

BACKGROUND: Panax notoginseng (Burk) F. H. Chen is one of the most famous Chinese traditional medicinal plants. The taproot is the main organ producing triterpenoid saponins, and its development is directly linked to the quality and yield of the harvested P. notoginseng. However, the mechanisms underlying the dynamic metabolic changes occurring during taproot development of P. notoginseng are unknown. RESULTS: We carried out metabolomic and transcriptomic analyses to investigate metabolites and gene expression during the development of P. notoginseng taproots. The differentially accumulated metabolites included amino acids and derivatives, nucleotides and derivatives, and lipids in 1-year-old taproots, flavonoids and terpenoids in 2- and 3-year-old taproots, and phenolic acids in 3-year-old taproots. The differentially expressed genes (DEGs) are related to phenylpropanoid biosynthesis, metabolic pathway and biosynthesis of secondary metabolites at all three developmental stages. Integrative analysis revealed that the phenylpropanoid biosynthesis pathway was involved in not only the development of but also metabolic changes in P. notoginseng taproots. Moreover, significant accumulation of triterpenoid saponins in 2- and 3-year-old taproots was highly correlated with the up-regulated expression of cytochrome P450s and uridine diphosphate-dependent glycosyltransferases genes. Additionally, a gene encoding RNase-like major storage protein was identified to play a dual role in the development of P. notoginseng taproots and their triterpenoid saponins synthesis. CONCLUSIONS: These results elucidate the molecular mechanism underlying the accumulation of and change relationship between primary and secondary metabolites in P. notoginseng taproots, and provide a basis for the quality control and genetic improvement of P. notoginseng.


Assuntos
Panax notoginseng , Saponinas , Triterpenos , Panax notoginseng/genética , Metaboloma , Perfilação da Expressão Gênica
13.
BMC Med Genomics ; 17(1): 71, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443925

RESUMO

BACKGROUND: The timely and accurate diagnosis of bloodstream infection (BSI) is critical for patient management. With longstanding challenges for routine blood culture, metagenomics is a promising approach to rapidly provide sequence-based detection and characterisation of bloodborne bacteria. Long-read sequencing technologies have successfully supported the use of clinical metagenomics for syndromes such as respiratory illness, and modified approaches may address two requisite factors for metagenomics to be used as a BSI diagnostic: depletion of the high level of host DNA to then detect the low abundance of microbes in blood. METHODS: Blood samples from healthy donors were spiked with different concentrations of four prevalent causative species of BSI. All samples were then subjected to a modified saponin-based host DNA depletion protocol and optimised DNA extraction, whole genome amplification and debranching steps in preparation for sequencing, followed by bioinformatical analyses. Two related variants of the protocol are presented: 1mL of blood processed without bacterial enrichment, and 5mL of blood processed following a rapid bacterial enrichment protocol-SepsiPURE. RESULTS: After first identifying that a large proportion of host mitochondrial DNA remained, the host depletion process was optimised by increasing saponin concentration to 3% and scaling the reaction to allow more sample volume. Compared to non-depleted controls, the 3% saponin-based depletion protocol reduced the presence of host chromosomal and mitochondrial DNA < 106 and < 103 fold respectively. When the modified depletion method was further combined with a rapid bacterial enrichment method (SepsiPURE; with 5mL blood samples) the depletion of mitochondrial DNA improved by a further > 10X while also increasing detectable bacteria by > 10X. Parameters during DNA extraction, whole genome amplification and long-read sequencing were also adjusted, and subsequently amplicons were detected for each input bacterial species at each of the spiked concentrations, ranging from 50-100 colony forming units (CFU)/mL to 1-5 CFU/mL. CONCLUSION: In this proof-of-concept study, four prevalent BSI causative species were detected in under 12 h to species level (with antimicrobial resistance determinants) at concentrations relevant to clinical blood samples. The use of a rapid and precise metagenomic protocols has the potential to advance the diagnosis of BSI.


Assuntos
Saponinas , Sepse , Humanos , DNA Mitocondrial , Metagenômica , Mitocôndrias
14.
Physiol Plant ; 176(2): e14260, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38511471

RESUMO

Bacosides are dammarane-type triterpenoidal saponins in Bacopa monnieri and have various pharmacological applications. All the bacosides are diversified from two isomers, i.e., jujubogenin and pseudojujubogenin. The biosynthetic pathway of bacoside is not well elucidated. In the present study, we characterized a UDP-glycosyltransferase, UGT79A18, involved in the glycosylation of pseudojujubogenin. UGT79A18 shows higher expression in response to 5 h of wounding, and 3 h of MeJA treatment. The recombinant UGT79A18 shows in vitro activity against a wide range of flavonoids and triterpenes and has a substrate preference for protopanaxadiol, a dammarane-type triterpene. Secondary metabolite analysis of overexpression and knockdown lines of UGT79A18 in B. monnieri identify bacopasaponin D, bacopaside II, bacopaside N2 and pseudojujubogenin glucosyl rhamnoside as the major bacosides that were differentially accumulated. In the overexpression lines of UGT79A18, we found 1.7-fold enhanced bacopaside II, 8-fold enhanced bacopasaponin D, 3-fold enhanced pseudojujubogenin glucosyl rhamnoside, and 1.6-fold enhanced bacopaside N2 content in comparison with vector control plant, whereas in the knockdown lines of UGT79A18, we found 1.4-fold reduction in bacopaside II content, 3-fold reduction in the bacopasaponin D content, 2-fold reduction in the pseudojujubogenin glucosyl rhamnoside content, and 1.5-fold reduction in bacopaside N2 content in comparison with vector control. These results suggest that UGT79A18 is a significant UDP glycosyltransferase involved in glycosylating pseudojujubogenin and enhancing the pseudojujubogenin-derived bacosides.


Assuntos
Acetatos , Bacopa , Ciclopentanos , Oxilipinas , Saponinas , Triterpenos , Bacopa/genética , Bacopa/química , Glicosiltransferases/genética , Vias Biossintéticas , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Difosfato de Uridina , Extratos Vegetais/química
15.
CNS Neurosci Ther ; 30(2): e14581, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38421141

RESUMO

AIMS: We aimed to explore the role and molecular mechanism of polygalacic acid (PA) extracted from traditional Chinese medicine Polygala tenuifolia in the treatment of Alzheimer's disease (AD). METHODS: The network pharmacology analysis was used to predict the potential targets and pathways of PA. Molecular docking was applied to analyze the combination between PA and core targets. Aß42 oligomer-induced AD mice model and microglia were used to detect the effect of PA on the release of pro-inflammatory mediators and its further mechanism. In addition, a co-culture system of microglia and neuronal cells was constructed to assess the effect of PA on activating microglia-mediated neuronal apoptosis. RESULTS: We predict that PA might regulate inflammation by targeting PPARγ-mediated pathways by using network pharmacology. In vivo study, PA could attenuate cognitive deficits and inhibit the expression levels of inflammation-related factors. In vitro study, PA can also decrease the production of activated microglia-mediated inflammatory cytokines and reduce the apoptosis of N2a neuronal cells. PPARγ inhibitor GW9662 inversed the neuroprotective effect of PA. Both in vivo and in vitro studies showed PA might attenuate the inflammation through the PPARγ/NF-κB pathway. CONCLUSIONS: PA is expected to provide a valuable candidate for new drug development for AD in the future.


Assuntos
Disfunção Cognitiva , NF-kappa B , Ácido Oleanólico/análogos & derivados , Saponinas , Camundongos , Animais , NF-kappa B/metabolismo , PPAR gama , Simulação de Acoplamento Molecular , Transdução de Sinais , Inflamação/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Microglia
16.
Pharmacol Res ; 201: 107090, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309381

RESUMO

Depression is a major global health issue that urgently requires innovative and precise treatment options. In this context, saikosaponin has emerged as a promising candidate, offering a variety of therapeutic benefits that may be effective in combating depression. This review delves into the multifaceted potential of saikosaponins in alleviating depressive symptoms. We summarized the effects of saikosaponins on structural and functional neuroplasticity, elaborated the regulatory mechanism of saikosaponins in modulating key factors that affect neuroplasticity, such as inflammation, the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, and the brain-gut axis. Moreover, this paper highlights existing gaps in current researches and outlines directions for future studies. A detailed plan is provided for the future clinical application of saikosaponins, advocating for more targeted researches to speed up its transition from preclinical trials to clinical practice.


Assuntos
Ácido Oleanólico , Ácido Oleanólico/análogos & derivados , Saponinas , Depressão/tratamento farmacológico , Saponinas/farmacologia , Saponinas/uso terapêutico , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Plasticidade Neuronal
17.
Phytother Res ; 38(3): 1651-1680, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38299680

RESUMO

Drug development for atherosclerosis, the underlying pathological state of ischemic cardiovascular diseases, has posed a longstanding challenge. Saponins, classified as steroid or triterpenoid glycosides, have shown promising therapeutic potential in the treatment of atherosclerosis. Through an exhaustive examination of scientific literature spanning from May 2013 to May 2023, we identified 82 references evaluating 37 types of saponins in terms of their prospective impacts on atherosclerosis. These studies suggest that saponins have the potential to ameliorate atherosclerosis by regulating lipid metabolism, inhibiting inflammation, suppressing apoptosis, reducing oxidative stress, and modulating smooth muscle cell proliferation and migration, as well as regulating gut microbiota, autophagy, endothelial senescence, and angiogenesis. Notably, ginsenosides exhibit significant potential and manifest essential pharmacological attributes, including lipid-lowering, anti-inflammatory, anti-apoptotic, and anti-oxidative stress effects. This review provides a comprehensive examination of the pharmacological attributes of saponins in atherosclerosis, with particular emphasis on their role in the regulation of lipid metabolism regulation and anti-inflammatory effects. Thus, saponins may warrant further investigation as a potential therapy for atherosclerosis. However, due to various reasons such as low oral bioavailability, the clinical application of saponins in the treatment of atherosclerosis still needs further exploration.


Assuntos
Aterosclerose , Ginsenosídeos , Saponinas , Humanos , Saponinas/farmacologia , Estudos Prospectivos , Aterosclerose/tratamento farmacológico , Ginsenosídeos/farmacologia , Anti-Inflamatórios
18.
Chem Biol Interact ; 391: 110892, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38364601

RESUMO

Sodium aescinate (SA) is extracted from Aesculus wilsonii Rehd seeds and was first marketed as a medicament in German. With the wide application of SA in clinical practice, reports of adverse drug reactions and adverse events have gradually increased, including renal impairment. However, the pathogenic mechanisms of SA have not yet been fully elucidated. The toxic effects and underlying mechanisms of SA were explored in this study. Our data showed that SA significantly elevated the levels of blood urea nitrogen (BUN), serum creatinine (Scr) and Kidney injury molecule 1 (Kim-1), accompanied by pathologically significant changes in renal tissue. SA induced NRK-52E cell death and disrupted the integrity of the cell membrane. Moreover, SA caused significant reductions in FTH, Nrf2, xCT, GPX4, and FSP1 levels, but increased TFR1 and ACSL4 levels. SA decreased glutathione peroxidase (GPx), glutathione (GSH) and cysteine (Cys) levels, but improved Fe2+, malondialdehyde (MDA), reactive oxygen species (ROS) and lipid peroxidation levels, ultimately leading to the induction of ferroptosis. Importantly, inhibition of ferroptosis or activation of the Nrf2/GPX4 pathway prevented SA-induced nephrotoxicity. These findings indicated that SA induced oxidative damage and ferroptosis-mediated kidney injury by suppressing the Nrf2/GPX4 axis activity.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Ferroptose , Saponinas , Triterpenos , Humanos , Fator 2 Relacionado a NF-E2 , Glutationa
19.
J Ethnopharmacol ; 326: 117778, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38310990

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In China, the Chinese patent drug Realgar-Indigo naturalis Formula (RIF) is utilized for the therapy of acute promyelocytic leukemia (APL). Comprising four traditional Chinese herb-Realgar, Indigo naturalis, Salvia miltiorrhiza, and Pseudostellaria heterophylla-it notably includes tetra-arsenic tetra-sulfide, indirubin, tanshinone IIa, and total saponins of Radix Pseudostellariae as its primary active components. Due to its arsenic content, RIF distinctly contributes to the therapy for APL. However, the challenge of arsenic resistance in APL patients complicates the clinical use of arsenic agents. Interestingly, RIF demonstrates a high remission rate in APL patients, suggesting that its efficacy is not significantly compromised by arsenic resistance. Yet, the current state of research on RIF's ability to reverse arsenic resistance remains unclear. AIM OF THE STUDY: To investigate the mechanism of different combinations of the compound of RIF in reversing arsenic resistance in APL. MATERIALS AND METHODS: The present study utilized the arsenic-resistant HL60-PMLA216V-RARα cell line to investigate the effects of various RIF compounds, namely tetra-arsenic tetra-sulfide (A), indirubin (I), tanshinone IIa (T), and total saponins of Radix Pseudostellariae (S). The assessment of cell viability, observation of cell morphology, and evaluation of cell apoptosis were performed. Furthermore, the mitochondrial membrane potential, changes in the levels of PMLA216V-RARα, apoptosis-related factors, and the PI3K/AKT/mTOR pathway were examined, along with autophagy in all experimental groups. Meanwhile, we observed the changes about autophagy after blocking the PI3K or mTOR pathway. RESULTS: Tanshinone IIa, indirubin and total saponins of Radix Pseudostellariae could enhance the effect of tetra-arsenic tetra-sulfide down-regulating PMLA216V-RARα, and the mechanism was suggested to be related to inhibiting mTOR pathway to activate autophagy. CONCLUSIONS: We illustrated that the synergistic effect of different compound combinations of RIF can regulate autophagy through the mTOR pathway, enhance cell apoptosis, and degrade arsenic-resistant PMLA216V-RARα.


Assuntos
Abietanos , Arsênio , Arsenicais , Medicamentos de Ervas Chinesas , Leucemia Promielocítica Aguda , Saponinas , Humanos , Arsênio/efeitos adversos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/induzido quimicamente , Fosfatidilinositol 3-Quinases , Arsenicais/farmacologia , Arsenicais/uso terapêutico , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Saponinas/uso terapêutico
20.
Bioorg Chem ; 145: 107230, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387397

RESUMO

Historically, Astragalus membranaceus Bunge has been used as a beneficial medicinal plant, particularly in the Asian traditional medical systems, for the treatment of various human diseases such as stomach ulcers, diarrhea, and respiratory issues associated with phlegm. In this study, a phytochemical characterization of the aerial parts of A. membranaceusled to the isolation of 29 oleanane-type triterpenoid saponins, including 11 new compounds named astraoleanosides E-P (6-9, 13, 14, 18-22), as well as 18 known ones. The structures of these compounds were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. Among them, astraoleanoside H (9) and cloversaponin III (15) demonstrated the most potent ß-glucuronidase inhibitory activities, with IC50 values of 21.20 ± 0.75 and 9.05 ± 0.47 µM, respectively, compared to the positive control d-saccharic acid 1,4-lactone (IC50 = 20.62 ± 1.61 µM). Enzyme kinetics studies were then conducted to investigate the type of inhibition exhibited by these active compounds. In addition, the binding mechanism, key interactions, binding stability, and dynamic behavior of protein-ligand complexes were investigated through in silico approaches, such as molecular docking and molecular dynamics simulations. These findings highlight the promising potential of triterpenoid saponins from A. membranaceus as lead compounds for ß-glucuronidase inhibitors, offering new possibilities for the development of therapeutic agents targeting various diseases where ß-glucuronidase plays a crucial role.


Assuntos
Ácido Oleanólico , Ácido Oleanólico/análogos & derivados , Saponinas , Triterpenos , Humanos , Estrutura Molecular , Astragalus propinquus/química , Simulação de Acoplamento Molecular , Saponinas/química , Ácido Oleanólico/química , Componentes Aéreos da Planta/química , Triterpenos/farmacologia , Triterpenos/química
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