ABSTRACT
BACKGROUND: Monkeypox is an emerging infectious disease with confirmed cases and deaths in several parts of the world. In light of this crisis, this study aims to analyze the global knowledge pattern of monkeypox-related patents and explore current trends and future technical directions in the medical development of monkeypox to inform research and policy. METHODS: A comprehensive study of 1,791 monkeypox-related patents worldwide was conducted using the Derwent patent database by descriptive statistics, social network method and linear regression analysis. RESULTS: Since the 21st century, the number of monkeypox-related patents has increased rapidly, accompanied by increases in collaboration between commercial and academic patentees. Enterprises contributed the most in patent quantity, whereas the initial milestone patent was filed by academia. The core developments of technology related to the monkeypox include biological and chemical medicine. The innovations of vaccines and virus testing lack sufficient patent support in portfolios. CONCLUSIONS: Monkeypox-related therapeutic innovation is geographically limited with strong international intellectual property right barriers though it has increased rapidly in recent years. The transparent licensing of patent knowledge is driven by the merger and acquisition model, and the venture capital, intellectual property and contract research organization model. Currently, the patent thicket phenomenon in the monkeypox field may slow the progress of efforts to combat monkeypox. Enterprises should pay more attention to the sharing of technical knowledge, make full use of drug repurposing strategies, and promote innovation of monkeypox-related technology in hotspots of antivirals (such as tecovirimat, cidofovir, brincidofovir), vaccines (JYNNEOS, ACAM2000), herbal medicine and gene therapy.
Subject(s)
Communicable Diseases, Emerging , Mpox (monkeypox) , Vaccines , Humans , Communicable Diseases, Emerging/drug therapy , Communicable Diseases, Emerging/epidemiology , Mpox (monkeypox)/drug therapy , Mpox (monkeypox)/epidemiology , TechnologyABSTRACT
In light of the situation and the characteristics of Omicron, the country has continuously optimized the rules for the prevention and control of COVID-19. The global epidemic is still spreading, and new cases of infection continue to emerge in China. To facilitate the infected person to estimate the course of virus infection, a prediction model for predicting negative conversion time is proposed in this article. The clinical features of Omicron-infected patients in Shandong Province in the first half of 2022 are retrospectively studied. These features are grouped by disease diagnosis result, clinical sign, traditional Chinese medicine symptoms, and drug use. These features are input to the eXtreme Gradient Boosting (XGBoost) model, and the output is the predicted number of negative conversion days. At the same time, XGBoost is used as the underlying algorithm of the conformal prediction (CP) framework, which can realize the probability interval estimation with a controllable error rate. The results show that the proposed model has a mean absolute error of 3.54 days and has the shortest interval prediction result. This shows that the method in this paper can carry more decision-making information and help people better understand the disease and self-estimate the course of the disease to a certain extent.
ABSTRACT
This study was conducted to investigate the effects of dietary supplementation of 0%, 0.2%, 0.35%, and 0.5% cinnamon essential oil on growth performance, fatty acid, and fillet quality of tilapia (Oreochromis niloticus). The results of growth experiments showed that the weight gain rate linearly and quadratically increased with increasing cinnamon essential oil doses (p < 0.05). The results of fatty acids experiments showed that the addition of essential oil significantly decreased the saturated fatty acids levels from 36.67% to 30.82% and increased the polyunsaturated fatty acids (PUFA) levels from 24.55% to 46.89%; especially, the n - 3 PUFA of 0.5% essential oil treatment showed the highest levels. Moreover, the n - 6 PUFA of 0.2% essential oil treatment were increased from 22.17% to 32.99%. The results of fillet quality experiments showed that the hardness and cohesiveness were linearly and quadratically increased with the increasing essential oil doses on days 4 and 7, respectively. The b* values linearly and quadratically decreased as the doses increased on day 7 (p < 0.05). The total volatile basic nitrogen levels were quadratically decreased with increasing cinnamon essential oil doses on day 7 (p < 0.05). In general, it can be concluded that cinnamon essential oil presented positive effects on the growth, nutritive values, and meat quality in tilapia.
Subject(s)
Fatty Acids, Omega-3 , Oils, Volatile , Tilapia , Animals , Fatty Acids , Oils, Volatile/pharmacology , Cinnamomum zeylanicum , Meat/analysis , Dietary Supplements , Animal Feed/analysisABSTRACT
Osthole is a coumarin compound found in the traditional Chinese medicine Cnidium monnieri. Extensive studies have shown that osthole exhibits many medicinal properties, and recently, researchers have found that it possesses potent airway-relaxation activity by inhibiting phosphodiesterase 4D activity, making it a potential novel bronchodilator that does not target ß2-adrenoceptors for asthma treatment. Here, we report the complete biosynthesis of osthole in engineered yeast. We created an umbelliferone (UMB)-producing strain by reconstituting the complete UMB pathway in yeast. We found that coumarin synthase (COSY) is essential for the conversion of 2',4'-dihydroxycinnamoyl-CoA into UMB in yeast; this conversion has been treated as a spontaneous step in previously reported UMB-producing microbials. By introducing downstream prenyltransferase and methyltransferase genes and addressing problems such as protein expression and cofactor supply to fulfill the downstream steps, complete biosynthesis of osthole was achieved. Finally, through metabolic engineering, to ensure precursor supply, and the debugging of rate-limited steps, the osthole titer reached 108.10 mg/L in shake flasks and 255.1 mg/L in fed-batch fermentation. Our study is the first to produce osthole using engineered microbes, providing a blueprint for the supply of plant-derived osthole via microbial fermentation, which will remove the barriers of resource limitations for osthole-based drug development.
Subject(s)
Coumarins , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolism , Coumarins/metabolism , Coumarins/pharmacology , Fermentation , Signal Transduction , Metabolic EngineeringABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Curcumae Rhizoma-Sparganii Rhizoma (CR-SR) is a classic herbal pair to promote blood circulation and remove blood stasis in ancient China. However, the molecular mechanism is still unclear. AIM OF STUDY: To screen out the anti-liver fibrosis active ingredients in CR-SR. Moreover, preliminary exploration the molecular mechanism of CR-SR to ameliorates liver fibrosis. MATERIALS AND METHODS: In this research, plant taxonomy has been confirmed in the "The Plant List" database (www.theplantlist.org). The chemical components of CR-SR were analysed by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). "Component-Target-Pathway-Disease" network of CR-SR components were built by network pharmacology. Then, the interaction between primary components and predicted protein targets based on network pharmacology were validated by molecular docking. The pharmacological actions of CR-SR were verified by blood biochemical indexes, histopathologic examination of CCL4 induced rats' model. The core protein targets were verified by Western blot. The effects of screened active components by molecular autodocking were verified by HSC-T6 cell experiment. RESULTS: The result shows that 57 chemical constituents in CR-SR herbal pair were identified by UPLC-Q/TOF-MS, in which, 27 compounds were closely connected with liver fibrosis related protein targets. 55 protein targets screened out by "component-target-pathway-disease network" maybe the underlying targets for CR-SR to cure liver fibrosis. Moreover, the 55 protein targets are mainly related to RNA transcription, apoptosis, and signal transduction. The molecular autodocking predicted that ten components can bond well with PTGS2 and RELA protein targets. The blood biochemical indexes, histopathologic examination of CCL4 induced rats experiment showed that CR-SR has well intervention effect of liver fibrosis. The Western blot analysis indicated that CR-SR could significantly inhibit RELA, PTGS2, IL-6, SRC, and AKT1 protein expression to exert the anti-fibrosis effect. The HSC-T6 cell experiment indicated that both formononetin (FNT) and curdione could significantly inhibit the activation of HSC and reduce the expression of PTGS2, and p-AKT1 which was accordance with the molecular autodocking results. CONCLUSION: This study proved the molecular mechanism of CR-SR multi-component and multi-target anti-liver fibrosis effect through mass spectrometry, network pharmacology, and western blotting technology. The research provides a theoretical evidence for the development and utilization of CR-SR herbal pair.
Subject(s)
Drugs, Chinese Herbal , Rats , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/analysis , Molecular Docking Simulation , Network Pharmacology , Cyclooxygenase 2 , Rhizome/chemistryABSTRACT
High-temperature negative thermal quenching (NTQ) phosphors are crucial to high-performance light-emitting devices. Herein, we report the high-temperature NTQ effect in deep-red to near-infrared (NIR) emitting copper iodide cluster-based coordination polymers as unconventional phosphors, whose NTQ operating temperature can reach as high as 500 K, the highest temperature reached by NTQ molecular-based materials.
ABSTRACT
Rg2 and Re are both rhamnose-containing ginsenosides isolated exclusively from Panax plants, which exhibit broad spectrum of pharmacological activities. However, limitations of current plant-relied manufacturing methods have largely hampered their medical applications. Here, we report elucidation of the complete biosynthetic pathway of these two ginsenosides by the identification of a rhamnosyltransferase PgURT94 from Panax ginseng. We then achieve de novo bio-production of Rg2 and Re from glucose by reconstituting their biosynthetic pathways in yeast. Through stepwise strain engineering and fed-batch fermentation, the maximum yield of Rg2 and Re reach 1.3 and 3.6 g/L, respectively. Our work completes the identification of the last missing enzyme for Rg2 and Re biosynthesis and achieves their high-level production by engineered yeasts. Once scaled, this microbial biosynthesis platform will enable a robust and stable supply of Rg2 and Re and facilitate their food and medical applications.
Subject(s)
Ginsenosides , Panax , Biosynthetic Pathways , Fermentation , Ginsenosides/pharmacology , Saccharomyces cerevisiae/metabolismABSTRACT
The application of chemically modified biochar is a promising strategy for the remediation of contaminated (e.g., pesticides) soil. In this study, H3PO4 was used to modify peanut shell to improve the remediation performance of biochar. Surface area (980.19 m2/g), pore volume (0.12 cm3/g), and the functional groups (OH, CO, and phosphorus-containing groups) on the biochar were increased by H3PO4 treatment. The sorption experimental data were well fitted by Freundlich model, while the sorption affinity (Kf) of H3PO4 modified biochar (PBC) for atrazine was 128 times greater than that of the untreated biochar (BC) in the aquatic systems. The Kf values of PBC-amended soil to atrazine were increased by 13.57 times than that of single soil. The strong sorption of PBC on atrazine delayed the degradation of atrazine in soil, and the residual percentage of atrazine in soil and soil-PBC mixture were 4.90% and 71.44% at the end of 60-day incubation, with the degradation half-life increased from 13.3 to 121.6 d. The analysis of high-throughput sequencing results showed that atrazine reduced the diversity of soil microbial community, but the abundance of microorganisms with degradation function increased and became dominant species. The addition of PBC in soil accelerated the microbial remediation of atrazine stress, which may promote the soil nitrogen cycle. Therefore, amendment of atrazine contaminated soil with PBC can reduce the environmental risk of atrazine and benefit the soil microbial ecology.
Subject(s)
Atrazine , Environmental Restoration and Remediation , Pesticides , Soil Pollutants , Atrazine/analysis , Soil Pollutants/analysis , Adsorption , Charcoal/chemistry , Soil/chemistry , Bacteria , PhosphorusABSTRACT
Magnetotactic bacteria are ubiquitous microorganisms in nature that synthesize intracellular magnetic nanoparticles called magnetosomes in a gene-controlled way and arrange them in chains. From in vitro to in vivo, we demonstrate that the intact body of Magnetospirillum magneticum AMB-1 has potential as a natural magnetic hyperthermia material for cancer therapy. Compared to chains of magnetosomes and individual magnetosomes, the entire AMB-1 cell exhibits superior heating capability under an alternating magnetic field. When incubating with tumor cells, the intact AMB-1 cells disperse better than the other two types of magnetosomes, decreasing cellular viability under the control of an alternating magnetic field. Furthermore, in vivo experiments in nude mice with neuroblastoma found that intact AMB-1 cells had the best antitumor activity with magnetic hyperthermia therapy compared to other treatment groups. These findings suggest that the intact body of magnetotactic bacteria has enormous promise as a natural material for tumor magnetic hyperthermia. In biomedical applications, intact and living magnetotactic bacteria play an increasingly essential function as a targeting robot due to their magnetotaxis.
Subject(s)
Hyperthermia, Induced , Magnetosomes , Neuroblastoma , Animals , Magnetic Fields , Magnetosomes/metabolism , Mice , Mice, Nude , Neuroblastoma/metabolism , Neuroblastoma/therapyABSTRACT
OBJECTIVE: To evaluate the efficacy and safety outcome and related risk factors of Naoxueshu in the treatment of acute SICH. METHODS: Two hundred twenty patients were enrolled in this study. Diagnosis of SICH was based on neuroimaging. All the patients received regular treatment and Naoxueshu oral liquid 10 ml 3 times a day for 14 consecutive days. Surgical intervention was conducted as needed. Efficacy and safety outcomes were evaluated. RESULTS: Hematoma volume decreased significantly 7 days after Naoxueshu treatment (from 27.3 ± 20.0 to 15.1 ± 15.1 ml, P < 0.0001), and it decreased further in 14-day result (6.9 ± 10.4 ml, P < 0.0001). Patients' neurological function was improved remarkably with NIHSS scores from baseline 13 points to 7-day 7 points (P < 0.0001) and 14-day 4 points (P < 0.0001). Cerebral edema was relieved only 14 days after Naoxueshu treatment (from 3 to 2 points, P < 0.0001). No clinically significant change was found in 7-day and 14-day safety results. Female sex was related independently to large 7-day hematoma volume and worse 7-day NIHSS score while it would not affect patients' 14-day outcomes. Rare cause of SICH (B = 17.4, P = 0.009) alone was related to large 14-day hematoma volume. Worse baseline NIHSS score (B = 0.3, P = 0.003) and early use of Naoxueshu (B = 2.9, P = 0.005) were related to worse 7-day and14-day neurological function. CONCLUSION: Naoxueshu oral liquid could relieve hematoma volume and cerebral edema safely; meanwhile, it could improve patients' neurological function. Sex, cause of SICH, and time from onset to receive Naoxueshu should be taken into consideration in the treatment of SICH.
Subject(s)
Brain Edema , Cerebral Hemorrhage , Brain Edema/diagnostic imaging , Brain Edema/drug therapy , Brain Edema/etiology , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/drug therapy , Female , Hematoma/complications , Humans , Risk Factors , Treatment OutcomeABSTRACT
The Chinese medicinal plant Panax notoginseng has been traditionally used to activate blood flow and circulation, and to prevent blood stasis. P. notoginseng contains protopanaxatriol (PPT)-type saponins as its main active compounds, thus distinguishing it from the other two famous Panax species, P. ginseng and P. quinquefolius. Ginsenoside Rg1 (Rg1), notoginsenoside R1 (NgR1), and notoginsenoside R2 (NgR2) are three major PPT-type saponins in P. notoginseng and possess potential cardiovascular protection activities. However, their use in medical applications has long been hampered by the lack of sustainable and low-cost industrial-scale preparation methods. In this study, a PPT-producing yeast chassis strain was designed and constructed based on a previously constructed and optimized protopanaxadiol (PPD)-producing Saccharomyces cerevisiae strain, and further optimized by systemically engineering and optimizing the expression level of its key P450 biopart. Rg1-producing yeast strains were constructed by introducing PgUGT71A53 and PgUGT71A54 into the PPT chassis strain. The fermentation titer of Rg1 reached 1.95 g/L. A group of UDP-glycosyltransferases (UGT) from P. notoginseng and P. ginseng were characterized, and were found to generate NgR1 and NgR2 by catalyzing the C6-O-Glc xylosylation of Rg1 and Rh1, respectively. Using one of these UGTs, PgUGT94Q13, and the previously identified PgUGT71A53 and PgUGT71A54, the biosynthetic pathway to produce saponins NgR1 and NgR2 from PPT could be available. The NgR1 cell factory was further developed by introducing PgUGT94Q13 and a heterologous UDP-xylose biosynthetic pathway from Arabidopsis thaliana into the highest Rg1-producing cell factory. The NgR2-producing cell factory was constructed by introducing PgUGT71A54, PgUGT94Q13, and the UDP-xylose biosynthetic pathway into the PPT chassis. De novo production of NgR1 and NgR2 reached 1.62 g/L and 1.25 g/L, respectively. Beyond the realization of artificial production of the three valuable saponins Rg1, NgR1, and NgR2 from glucose, our work provides a green and sustainable platform for the efficient production of other PPT-type saponins in engineered yeast strains, and promotes the industrial application of PPT-type saponins as medicine and functional foods.
Subject(s)
Ginsenosides , Panax notoginseng , Panax , Saponins , Glycosyltransferases/genetics , Panax/genetics , Panax notoginseng/genetics , Saccharomyces cerevisiae/genetics , SapogeninsABSTRACT
Icaritin is a prenylflavonoid present in the Chinese herbal medicinal plant Epimedium spp. and is under investigation in a phase III clinical trial for advanced hepatocellular carcinoma. Here, we report the biosynthesis of icaritin from glucose by engineered microbial strains. We initially designed an artificial icaritin biosynthetic pathway by identifying a novel prenyltransferase from the Berberidaceae-family species Epimedium sagittatum (EsPT2) that catalyzes the C8 prenylation of kaempferol to yield 8-prenlykaempferol and a novel methyltransferase GmOMT2 from soybean to transfer a methyl to C4'-OH of 8-prenlykaempferol to produce icaritin. We next introduced 11 heterologous genes and modified 12 native yeast genes to construct a yeast strain capable of producing 8-prenylkaempferol with high efficiency. GmOMT2 was sensitive to low pH and lost its activity when expressed in the yeast cytoplasm. By relocating GmOMT2 into mitochondria (higher pH than cytoplasm) of the 8-prenylkaempferol-producing yeast strain or co-culturing the 8-prenylkaempferol-producing yeast with an Escherichia coli strain expressing GmOMT2, we obtained icaritin yields of 7.2 and 19.7 mg/L, respectively. Beyond the characterizing two previously unknown plant enzymes and conducting the first biosynthesis of icaritin from glucose, we describe two strategies of overcoming the widespread issue of incompatible pH conditions encountered in basic and applied bioproduction research. Our findings will facilitate industrial-scale production of icaritin and other prenylflavonoids.
Subject(s)
Liver Neoplasms , Saccharomyces cerevisiae , Humans , Saccharomyces cerevisiae/genetics , Escherichia coli/genetics , Liver Neoplasms/metabolism , Glucose/metabolismABSTRACT
In this work, spiral dextrin/resveratrol (SD/Res) crystal, a new colon-specific drug-delivery system, was established by a novel method of encapsulation and cocrystallization to improve the antidigestion ability compared with the SD/Res inclusion complex (SD/Res IC) prepared by encapsulation and coprecipitation. X-ray diffraction (XRD) and scanning electron microscopy (SEM) revealed that the SD/Res crystal formed a more regular and perfect crystallite than SD/Res IC. Moreover, the encapsulation ability and thermostability of the SD/Res crystal were enhanced as the chain length of SD was increased. In vitro digestion indicated that SD/Res IC merely achieved small intestine-targeted release of resveratrol, while the SD/Res crystal could act as a colon-specific delivery system to protect resveratrol from degradation by gastric acid and pancreatic enzymes. The SD-1/Res crystal presented much higher thermal stability and stronger gastrointestinal stability than other SD/Res crystals and SD/Res ICs, which facilitated its application as a novel colon-target delivery system for resveratrol.
Subject(s)
Colon/drug effects , Dextrins/chemistry , Drug Delivery Systems/methods , Plant Extracts/chemistry , Resveratrol/chemistry , Resveratrol/pharmacology , Drug Compounding , Drug Liberation , Humans , Particle Size , X-Ray Diffraction , Zea mays/chemistryABSTRACT
OBJECTIVES: Surgical treatment is expected to remove clot immediately in acute spontaneous intracerebral hemorrhage (SICH) patients. The aim of this study was to evaluate whether Naoxueshu could enhance the efficacy of clot removal surgery in acute SICH patients. METHODS: One hundred twenty patients who had been diagnosed as SICH according to neuroimaging were enrolled in this study. They received craniotomy, decompressive craniectomy, or minimally invasive surgical evacuation as appropriate and then were randomized into two groups: the Naoxueshu group (NXS group, n = 60) and the control group (n = 60). All the patients received standard medical management while patients in NXS group also took Naoxueshu oral liquid 10 ml with three times a day for seven consecutive days. The primary outcome was the 7-day hematoma volume and secondary outcomes were 7-day National Institutes of Health Stroke Scale (NIHSS) score and 7-day cerebral edema score. RESULTS: After clot removal surgery, hematoma volume in NXS group (9.5 ± 8.0) was significantly decreased than that in Control group (21.3 ± 22.9, p < .0001) 7 days after surgery. Moreover, cerebral edema was also relieved after 7-day's Naoxueshu treatment (2.5 ± 0.9 vs. 2.9 ± 0.7, p = .043). Since patients in NXS group had worse baseline NIHSS score (17.2 ± 8.1 vs. 13.7 ± 10.1, p = .039), it was reasonable to conclude that Naoxueshu treatment could improve patients' neurological function because 7-day NIHSS score of the two groups was similar. CONCLUSION: Naoxueshu oral liquid could relieve hematoma volume and cerebral edema after clot removal surgery in acute SICH patients. Moreover, it had the potential to improve patients' short-term neurological function.
Subject(s)
Brain Edema , Cerebral Hemorrhage , Brain Edema/diagnostic imaging , Brain Edema/etiology , Cerebral Hemorrhage/diagnostic imaging , Craniotomy , Hematoma/surgery , Humans , Treatment OutcomeABSTRACT
More than 150 ginsenosides have been isolated and identified from Panax plants. Ginsenosides with different glycosylation degrees have demonstrated different chemical properties and bioactivity. In this study, we systematically cloned and characterized 46 UGT94 family UDP-glycosyltransferases (UGT94s) from a mixed Panax ginseng/callus cDNA sample with high amino acid identity. These UGT94s were found to catalyze sugar chain elongation at C3-O-Glc and/or C20-O-Glc of protopanaxadiol (PPD)-type, C20-O-Glc or C6-O-Glc of protopanaxatriol (PPT)-type or both C3-O-Glc of PPD-type and C6-O-Glc of PPT-type or C20-O-Glc of PPD-type and PPT-type ginsenosides with different efficiencies. We also cloned 26 and 51 UGT94s from individual P. ginseng and P. notoginseng plants, respectively; our characterization results suggest that there is a group of UGT94s with high amino acid identity but diverse functions or catalyzing activities even within individual plants. These UGT94s were classified into three clades of the phylogenetic tree and consistent with their catalytic function. Based on these UGT94s, we elucidated the biosynthetic pathway of a group of ginsenosides. Our present results reveal a series of UGTs involved in second sugar chain elongation of saponins in Panax plants, and provide a scientific basis for understanding the diverse evolution mechanisms of UGT94s among plants.
Subject(s)
Ginsenosides/biosynthesis , Glycosyltransferases/genetics , Panax/enzymology , Biosynthetic Pathways , Ginsenosides/metabolism , Glycosylation , Glycosyltransferases/metabolism , Panax/genetics , Panax/metabolism , Phylogeny , Uridine Diphosphate/metabolismABSTRACT
The hypothalamus-pituitary-ovary (HPO) axis plays fundamental roles in female neuroendocrinology and reproduction. Pituitary gonadotropins are located in the center of this axis. Previous investigation suggested that miR-7 is closely linked with gonadotropins. However, the interaction between miR-7 and the HPO axis remains unclear. This study aims to determine whether and how miR-7 functions in this axis. A mouse ovariectomy model and mouse primary pituitary cells were used in this study. The results showed that miR-7 is localized to gonadotrophs and somatotrophs. miR-7 can inhibit the expression, synthesis and secretion of gonadotropins, but not growth hormones. Gonadotropin-releasing hormone (GnRH) has inhibitory effects on miR-7, while estrogen enhances miR-7 expression. miR-7 is vital for the pathway by which GnRH and estrogen regulate gonadotropins by targeting v-raf-leukemia viral oncogene 1 (Raf1). Together, these results indicate that miR-7 acts as a potential switch in the feedback loop of the HPO axis by regulating gonadotropins.
Subject(s)
Gonadotropins/metabolism , Hypothalamus/metabolism , MicroRNAs/genetics , Ovary/metabolism , Pituitary Gland/cytology , Proto-Oncogene Proteins c-raf/genetics , Animals , Cells, Cultured , Estrogens/metabolism , Feedback, Physiological , Female , Gene Expression Regulation , Gonadotropin-Releasing Hormone/metabolism , Gonadotropins/genetics , Mice , Models, Animal , Ovariectomy , Ovary/surgery , Pituitary Gland/metabolism , Primary Cell CultureABSTRACT
In this study, the structure characteristics and the hypoglycemic and antioxidant activities of mulberry fruit polysaccharides obtained by the commonly used hot water (MFPh)-, ultrasonic (MFPu)-, acid (MFPc)- and alkali (MFPa)-assisted extraction methods were investigated. NMR analysis indicated that the four polysaccharides had similar glycosidic linkage patterns. Scanning electron microscopy analyses showed that the surface morphology of the polysaccharides was greatly affected by the extraction methods. The results of the bioactivity assays indicated that MFPh exhibited stronger antioxidant and α-amylase inhibitory activities than the other polysaccharides. Moreover, all the polysaccharides showed good α-glucosidase inhibitory activities except for MFPu with the lowest molecular weight. These results suggested that acid, alkali, and ultrasonic-assisted extractions have different effects on the degradation of polysaccharides without changing the main structure compared with hot water extraction. In addition, the molecular weight of polysaccharides plays a key role in the bioactivity of the mulberry fruit polysaccharides.
Subject(s)
Chemical Fractionation/methods , Morus/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Antioxidants/chemistry , Antioxidants/isolation & purification , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Fruit/chemistry , Glucose/chemistry , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Molecular Weight , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/chemistry , alpha-Glucosidases/chemistryABSTRACT
There is growing evidence that neuroinflammation is closely linked to depression. Honokiol, a biologically active substance extracted from Magnolia officinalis, which is widely used in traditional Chinese medicine, has been shown to exert significant anti-inflammatory effects and improve depression-like behavior caused by inflammation. However, the specific mechanism of action of this activity is still unclear. In this study, the lipopolysaccharide (LPS) mouse model was used to study the effect of honokiol on depression-like behavior induced by LPS in mice and its potential mechanism. A single administration of LPS (1 mg/kg, intraperitoneal injection) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), without affecting autonomous activity. Pretreatment with honokiol (10 mg/kg, oral administration) for 11 consecutive days significantly improved the immobility time of depressed mice in the FST and TST experiments. Moreover, honokiol ameliorated LPS-induced NF-κB activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and interferon γ (IFN-γ). In addition, honokiol inhibited LPS-induced indoleamine 2,3-dioxygenase (IDO) activation and quinolinic acid (a toxic product) increase and reduced the level of free calcium in brain tissue, thereby inhibiting calcium overload. In summary, our results indicate that the anti-depressant-like effects of honokiol are mediated by its anti-inflammatory effects. Honokiol may inhibit the LPS-induced neuroinflammatory response through the NF-κB signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.
Subject(s)
Antidepressive Agents/therapeutic use , Biphenyl Compounds/therapeutic use , Depression/drug therapy , Lignans/therapeutic use , Animals , Antidepressive Agents/pharmacology , Autonomic Nervous System/drug effects , Biphenyl Compounds/pharmacology , Brain/metabolism , Calcium/metabolism , Cytokines/blood , Depression/physiopathology , Disease Models, Animal , Hindlimb Suspension , Immobilization , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Inflammation Mediators/blood , Kynurenine/metabolism , Lignans/pharmacology , Lipopolysaccharides , Mice, Inbred ICR , NF-kappa B/genetics , NF-kappa B/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Swimming , Tryptophan/metabolismABSTRACT
Spiral dextrin subfraction (SD-40) obtained through enzyme debranching and gradient ethanol precipitation could interact with vitamin E (VE) or soy isoflavone (SIO) to form V-type inclusion complexes. The formation of two inclusion complexes was confirmed by Fourier transform-infrared spectroscopy, atomic force microscopy, and differential scanning calorimetry. In this study, an in vitro gastrointestinal model was used to investigate the breakdown of inclusion complexes and release behavior of bioactive compounds. The results indicated that the two inclusion complexes exhibited a controlled and sustained release behavior during digestion. In addition, the SD-40/VE inclusion complex presented higher stability and stronger antioxidant capacity than the SD-40/SIO inclusion complex. Furthermore, the first and zero order models were applied to understand the release kinetics of VE and SIO from inclusion complexes in the stomach, whereas the first order model was chosen to describe the release of VE and SIO from inclusion complexes in the intestine.
Subject(s)
Antioxidants/chemistry , Dextrins/chemistry , Drug Compounding/methods , Gastrointestinal Tract/metabolism , Isoflavones/chemistry , Plant Extracts/chemistry , Vitamin E/chemistry , Vitamin E/metabolism , Antioxidants/metabolism , Calorimetry, Differential Scanning , Digestion , Drug Carriers/chemistry , Drug Compounding/instrumentation , Humans , Kinetics , Glycine max/chemistry , Spectroscopy, Fourier Transform InfraredABSTRACT
The biomineralized bacterial magnetic nanoparticles (BMPs) have been widely studied for biomedical applications with their magnetic properties and a layer of biomembrane. Herein, BMPs were firstly used for magnetically targeted photothermal cancer therapy in vivo. A self-build C-shaped bipolar permanent magnet was used for magnetic targeting though the generation of a high gradient magnetic field within a small target area. For in vitro simulated experiment, BMPs had a high retention rate in magnetically targeted region with different flow rates. In H22 tumor bearing mice, the magnetic targeting induced a 40% increase of BMPs retention in tumor tissues. In vivo photothermal therapy with 808 nm laser irradiation could induce a complete tumor elimination with magnetic targeting. These results indicated that the systematically administrated BMPs with magnetic targeting would be promising for photothermal cancer therapy.