Natural Active Substances Research Articles

Silibinin Induces Both Apoptosis and Necroptosis with Potential Anti-tumor Efficacy in Lung Cancer.

Lung cancer incidence is steadily on the rise, posing a growing threat to human health. The search for therapeutic drugs from natural active substance and elucidating their mechanism have been the focus of anti-tumor research. In our work, Silibinin (SiL) was chosen as a possible substance that could inhibit lung cancer. and its effects on inducing tumor cell death have been studied. CCK-8 analysis and morphological observation were used to assess the cytotoxic impacts of SiL on lung cancer cells in vitro. The alterations in mitochondrial membrane potential (MMP) and apoptosis rate of cells were detected by flow cytometry. The level of lactate dehydrogenase (LDH) release out of cells was measured. The expression changes of apoptosis or necroptosis-related proteins were detected using western blotting. Protein interactions among RIPK1, RIPK3 and MLKL were analyzed using the co-immunoprecipitation technique. In vivo, SiL was evaluated for its antitumor effects using LLC tumor-bearing mice with mouse lung cancer. With an increased dose of SiL, the proliferation ability of A549 cells was considerably inhibited, and the accompanying cell morphology changed. The results of flow cytometry showed that after SiL treatment, MMP levels decreased, and the proportion of cells undergoing apoptosis increased. The proteins associated with apoptosis were upregulated and activated. The amount of LDH released from the cells increased following SiL treatment, accompanied by augmented expression and phosphorylation levels of necroptosis-related proteins. The co-IP assay further confirmed necrosome formation induced by SiL. Furthermore, Necrosulfonamide (an MLKL inhibitor) increased the apoptotic rate of SiL-treated cells and aggravated the cytotoxic effect of SiL, indicating that necroptosis blockade could switch cell death to apoptosis and increase the inhibitory effect of SiL on A549 cells. In LLC-bearing mice, gastric administration of SiL significantly inhibited tumor growth. This study helped clarify the anti-tumor mechanism of SiL against lung cancer, elucidating its role in dual induction of apoptosis and necroptosis. In particular, necroptosis blockade could switch cell death to apoptosis and increase the inhibitory effect of SiL. Our work provided an experimental basis for the research on cell death induced by SiL and revealed its possible applications for improving the management of lung cancer.</p>.

Yeast Extract Peptides Alleviate Depression in Chronic Restraint Stress Rats by Alleviating Hippocampal Neuronal Apoptosis and Dysbiosis of the Gut Microbiota.

Depression as a global neurological disorder, and hippocampal neuronal apoptosis and disorders of the gut microbiota are closely related to it. This study aims to expose the ameliorative effect of enzyme peptides (AP) from brewer's yeast on depressive behavior caused by chronic restraint stress (CRS) in rats. After 4 weeks of AP intervention, a significant alleviation of depressive behavior in the sucrose preference test (SPT), forced swim test (FST), and light-dark test (LDT) is observed in depressed rats. AP ameliorates neuronal damage with increased the expression of the key CREB/BDNF/TrkB/Akt signaling pathway, which increases the levels of the monoamine neurotransmitters 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in the hippocampus, buffering hyperactivity of the hypothalamo-pituitary-adrenal axis (HPA), and decreasing the serum cortisol (CORT) and adrenocorticotropic hormone (ACTH) levels in rats. In addition, AP modulates the disruption of the rat gut microbiota by chronic restraint stress (CRS), and the changes in the abundance of Lactobacillus animalis and Lactobacillus johnsonii are probably the key for AP performing antidepressant benefits. A strong correlation is found between gut microbiota and biochemical markers of depression. AP, as a natural and safe active substance, has a positive effect in the treatment of depression.

Endophytic Fungus UJ3-2 from Urtica fissa: Antibacterial Activity and Mechanism of Action against Staphylococcus aureus

Taking the endophytic fungus UJ3-2, isolated from Urtica fissa, as the experimental material, this study aimed to explore the composition of its metabolites and the underlying mechanisms by which it inhibits Staphylococcus aureus. Initially, the MIC, MBC, inhibitory curves, biofilm growth, and extracellular nucleic acids and proteins of S. aureus in response to the metabolites were measured. Secondly, PI staining and SEM were used to evaluate the impact of the metabolites on the integrity of the cell wall and overall morphology of S. aureus. Additionally, UPLC-MS was employed to analyze the composition of the secondary metabolites. The UJ3-2 strain was identified as Xylaria grammica based on ITS sequencing and designated as Xylaria grammica UJ3-2. Our results revealed that the metabolites of UJ3-2 exhibited excellent in vitro antibacterial activity against S. aureus, with both MIC and MBC values of 3.125 mg/mL. The inhibitory curve confirmed that 1 MIC of UJ3-2 metabolites could completely inhibit the growth of S. aureus within 24 h. With increasing concentrations of UJ3-2 metabolites, the growth of S. aureus biofilms was significantly suppressed, and obvious leakage of nucleic acids and proteins was observed. PI fluorescence staining indicated that various concentrations of UJ3-2 metabolites disrupted the integrity of the S. aureus cell membrane. SEM observation revealed that the treated S. aureus surfaces became rough, and the bacteria shrank and adhered to each other, showing a dose-dependent effect. UPLC-MS analysis suggested that the main components of the fermented metabolites were 6-oxocineole (17.92%), (S)-2-acetolactate (9.91%), 3-methyl-cis,cis-muconate (4.36%), and 8-oxogeranial (3.17%). This study demonstrates that the endophytic fungus UJ3-2 exhibits remarkable in vitro antibacterial effects against S. aureus, primarily by enhancing the permeability of the S. aureus cell membrane, causing the leakage of its intracellular contents, and altering the bacterial surface morphology to inhibit the pathogen. The endophytic fungus UJ3-2 has a good antibacterial effect on S. aureus, which gives it certain application prospects in the screening and industrial production of new and efficient natural antibacterial active substances.

Pelargonic acid’s interaction with the auxin transporter PIN1: A potential mechanism behind its phytotoxic effects on plant metabolism

Pelargonic acid (PA) is a saturated fatty acid commonly found in several organisms, that is known for its phytotoxic effect and its use as bioherbicide for sustainable weed management. Although PA is already commercialised as bioherbicide, its molecular targets and mode of action is unknown according to the Herbicide Resistance Action Committee. Therefore, the aim of this work was focusing on the way this natural active substance impacts the plant metabolism of the model species Arabidopsis thaliana. PA caused increase of secondary and adventitious roots, as well as torsion, loss of gravitropism and phytotoxic effects. Moreover, PA altered the cellular arrangement and the PIN proteins activity. Computational simulations revealed that the intermolecular interactions between PA and the polar auxin transporter protein PIN1 are very similar to those established between the natural auxin IAA and PIN1. However, under intracellular conditions, the PA-PIN1 binding is more energetically stable than the IAA-PIN1. These results suggest that PA could act as an auxin-mimics bioherbicide. The exogenous application of PA would be responsible for the alterations observed both at structural and ultrastructural levels, which would be caused by the alteration on the transport of auxins into the plant, inducing root inhibition and ultimately total stop of root growth.

Rapid discovery of natural antioxidants in Hypericum japonicum: Dual roles of the liquid phase mobile phase as extraction and separation solvent

Hypericum japonicum is a traditional folk medicine with various bioactivities such as hepatoprotective, antioxidant, and anti-tumorous. The antioxidant effect of H. japonicum is one of the most prominent effects due to its responsibility for many of its activities. To clarify active natural substance, the antioxidant properties of H. japonicum were preliminarily assessed by ferric reducing–antioxidant power (FRAP), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and Oxygen radical absorbance capacity (ORAC), as well as superoxide dismutase (SOD). Then, a straightforward and effective method named online liquid extraction-high performance liquid chromatography combined with ABTS antioxidant assay and mass spectrometry (OLE-HPLC-ABTS/Q-TOF-MS) was developed to swiftly and directly discover the antioxidants in H. japonicum. Using mobile phase as extraction and separation reagent, coupled with online activity analysis and compounds identification by high-resolution MS, the online system enables rapid screening of natural antioxidant bioactives from complex mixture. By using it, a total of 9 compounds including flavonoids and phenolic acids characterized by retention time, precise mass, and fragmentation ions in MS/MS spectra showed antioxidant action. Finally, the antioxidant and SOD activity of main found active compounds were validated by in vitro experiment assay and molecular docking. In summary, these results suggested that H. japonicum could be considered as a potential source of natural antioxidants, and the online integrated system might become a promising candidate for the natural antioxidants discovery in the future.

Effect of ultrasound combined with chemical pretreatment as an innovative non-thermal technology on the drying process, quality properties and texture of cherry subjected to radio frequency vacuum drying

To obtain high-quality cherry products, ultrasound (US) combined with five chemical pretreatment techniques were used on cherry prior to radio frequency vacuum drying (RFV), including carboxymethyl cellulose coating (CMC), cellulase (CE), ethanol (EA), isomaltooligosaccharide (IMO), and potassium carbonate + ethyl oleate (PC + AEEO). The effect of different pretreatments (US-CMC, US-CE, US-EA, US-IMO, US-(PC + AEEO)) on the drying characteristics, quality properties, texture, and sensory evaluation of cherries was evaluated. Results showed that the dehydration time and energy consumption were decreased by 4.17 − 20.83 % and 3.22 − 19.34 %, respectively, and the contents of individual sugars, soluble solid, total phenolics (TPC), natural active substances, total flavonoids (TFC), and antioxidant properties (DPPH, ABTS and FRAP) were significantly increased after US combined with five chemical treatments (P < 0.05). Moreover, the pretreatment played important role in improving texture properties and surface color retention in the dried cherries. According to the sensory evaluation analysis, the dehydrated cherries pretreated with US-CMC exhibited the highest overall acceptance, texture, crispness, color, and sweet taste showed lower off-odor, bitter taste and sour taste compared to control and other pretreatments. The findings indicate that US-CMC pretreatment is a promising technique for increasing physicochemical qualities and dehydration rate of samples, which provides a novel strategy to processing of dried cherry.

Research Progress on using Omics Technology to Examine the Antimicrobial Mechanisms of Natural Active Substances

Pathogenic microbial metabolism during food storage can lead to food spoilage, which can cause food poisoning and foodborne infections, posing a significant risk to human health and safety. Additionally, food spoilage generates greenhouse gases, which could contribute to global warming and have significant impacts. These challenges prompt us to explore effective solutions to reduce food spoilage, aiming to mitigate its adverse impacts. Many secondary plant metabolites have been used in the food and pharmaceutical industries due to their natural antimicrobial activity and low drug resistance. However, the reported targets of antibacterial action are complex, and with the continuous development of research methods, it has become possible to deeply analyze the antibacterial mechanisms using omics technologies. This article discussed the trends and application of transcriptomics, metabolomics, and proteomics in investigating the antimicrobial and antifungal properties of essential oils (EOs) and their active ingredients, aiming to provide a theoretical basis for the use of plant EOs and their active ingredients in addressing health risks and environmental challenges posed by food spoilage.

Efficient degradation of levofloxacin using peroxymonosulfate activated by a novel magnetic catalyst derived from waste walnut shell biomass

Developing an economical and efficient catalyst derived from biochar and metal-organic frameworks (MOFs) for the activation of peroxymonosulfate (PMS) to degrade pollutants holds promise for practical applications. Herein, a simple in-situ synthesis method was designed to generate zeolitic imidazole framework with Co-based (ZIF-67) on the surface of waste walnut shell biomass, and novel derived magnetic catalysts (BC@CobC, Biochar@Co base Carbon) were obtained by high-temperature carbonization. This structure could avoid the drawbacks of structural collapse and particle agglomeration of MOF derivatives, while the presence of biochar could accelerate electron transfer and improve the activation performance. For the degradation of levofloxacin, the removal rate in the 0.5-BC@CobC/PMS system reached 89.88 % in 15 min with a mineralization of 60.43 % when the dosage of catalyst was 0.01 g L−1. Capture experiments and EPR tests showed that SO4−•, •OH, •O2− and 1O2 were jointly participated in the levofloxacin degradation process. Meanwhile, the BC@CobC/PMS system was minimally affected by the pH, co-existing inorganic anions, and natural active substances. It is worth noting that the BC@CobC/PMS system also had excellent removal effect on other typical organic pollutants, and the removal rate could reach 100 %. Cycling experiments showed that BC@CobC maintained high catalytic activity after multiple recycling. The degradation pathway of levofloxacin was also analyzed. Compared to the existing reports, the catalyst is economically superior, with much improved pollutant removal, and boasts a lower catalyst usage. This work will provide a viable idea in terms of reusing biomass waste and activating PMS for wastewater treatment.

Potential therapeutic agents of Bombyx mori silk cocoon extracts from agricultural product for inhibition of skin pathogenic bacteria and free radicals.

Pathogenic bacteria are the cause of most skin diseases, but issues such as resistance and environmental degradation drive the need to research alternative treatments. It is reported that silk cocoon extract possesses antioxidant properties. During silk processing, the degumming of silk cocoons creates a byproduct that contains natural active substances. These substances were found to have inhibitory effects on bacterial growth, DNA synthesis, the pathogenesis of hemolysis, and biofilm formation. Thus, silk cocoon extracts can be used in therapeutic applications for the prevention and treatment of skin pathogenic bacterial infections. The extract of silk cocoons with pupae (SCP) and silk cocoons without pupae (SCWP) were obtained by boiling with distilled water for 9 h and 12 h, and were compared to silkworm pupae (SP) extract that was boiled for 1 h. The active compounds in the extracts, including gallic acid and quercetin, were determined using high-performance liquid chromatography (HPLC). Furthermore, the total phenolic and flavonoid content in the extracts were investigated using the Folin-Ciocalteu method and the aluminum chloride colorimetric method, respectively. To assess antioxidant activity, the extracts were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Additionally, the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of silk extracts and phytochemical compounds were determined against skin pathogenic bacteria. This study assessed the effects of the extracts and phytochemical compounds on growth inhibition, biofilm formation, hemolysis protection, and DNA synthesis of bacteria. The HPLC characterization of the silk extracts showed gallic acid levels to be the highest, especially in SCP (8.638-31.605 mg/g extract) and SP (64.530 mg/g extract); whereas quercetin compound was only detected in SCWP (0.021-0.031 mg/g extract). The total phenolics and flavonoids in silk extracts exhibited antioxidant and antimicrobial activity. Additionally, SCP at 9 h and 12 h revealed the highest anti-bacterial activity, with the lowest MIC and MBC of 50-100 mg/mL against skin pathogenic bacteria including Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Cutibacterium acnes and Pseudomonas aeruginosa. Hence, SCP extract and non-sericin compounds containing gallic acid and quercetin exhibited the strongest inhibition of both growth and DNA synthesis on skin pathogenic bacteria. The suppression of bacterial pathogenesis, including preformed and matured biofilms, and hemolysis activity, were also revealed in SCP extract and non-sericin compounds. The results show that the byproduct of silk processing can serve as an alternative source of natural phenolic and flavonoid antioxidants that can be used in therapeutic applications for the prevention and treatment of pathogenic bacterial skin infections.

STUDY OF ACUTE AND SUB-ACUTE TOXICITY OF A MEDICATION BASED ON SPIDER VENOM EXTRACT

Homeopathy is a regulatory therapy. The effectiveness of homeopathic therapy does not depend on the dose of the drug, but on the frequency of its repetitions. The composition of homeopathic preparations includes a wide range of natural and synthetic active substances: minerals; chemical substances; substances of plant origin; microorganisms, including fungi, bacteria, viruses, and plant parasites; substances of animal origin; and human materials, which may include tissues, secretions, hormones, and genetically homogeneous cell lines. One such substance is an extract of spider venom (Tarantul cubensis D6), which remains active in pharmaceutical preparation for a long time. The drug is selectively absorbed in inflamed tissues, differentiating them from healthy cells and suppressing inflammation. The drug is also effective in necrotic and proliferative processes. It is used for the treatment of panaritium in the initial stage, skin ulcers, necrobacillosis, and necrosis of the soft tissues of the animal. Any materials of animal or human origin are potentially dangerous for human and animal health, as they may contain toxic or pathogenic substances. Therefore, the study of the acute and subacute toxicity of spider venom extract is one of the stages of establishing the toxicological parameters of the drug. The use of the drug in a therapeutic dose caused an increase in animal body weight, hemoglobin concentration, number of leukocytes, erythrocytes, hematocrit value, average erythrocyte volume (MCV), average hemoglobin content in erythrocytes (МСН), average concentration of hemoglobin in erythrocytes (МСНС), number of platelets, and AST activity against the background of a slight decrease in total protein content, creatinine, urea, and ALT activity. The use of the drug in a 10-fold therapeutic dose caused an increase in animal body weight, creatinine, urea, ALT, and AST activity against the background of a decrease in the concentration of hemoglobin, the number of leukocytes and erythrocytes, the value of hematocrit, the average volume of erythrocytes (MCV), the average content of hemoglobin in erythrocytes (МСН), the average concentration of hemoglobin in erythrocytes (МСНС), the number of platelets, and the content of total protein.

Research Progress of Natural Active Substances with Immunosuppressive Activity.

The increasing prevalence of autoimmune diseases globally has prompted extensive research and the development of immunosuppressants. Currently, immunosuppressive drugs such as cyclosporine, rapamycin, and tacrolimus have been utilized in clinical practice. However, long-term use of these drugs may lead to a series of adverse effects. Therefore, there is an urgent need to explore novel drug candidates for treating autoimmune diseases. This review aims to find potential candidate molecules for natural immunosuppressive compounds derived from plants, animals, and fungi over the past decade. These compounds include terpenoids, alkaloids, phenolic compounds, flavonoids, and others. Among them, compounds 49, 151, 173, 200, 204, and 247 have excellent activity; their IC50 were less than 1 μM. A total of 109 compounds have good immunosuppressive activity, with IC50 ranging from 1 to 10 μM. These active compounds have high medicinal potential. The names, sources, structures, immunosuppressive activity, and the structure-activity relationship were summarized and analyzed.

Whey Protein Isolate as a Substrate to Design Calendula officinalis Flower Extract Controlled-Release Materials.

The use of natural active substances and the development of new formulations are promising directions in the cosmetic and pharmacy industries. The primary purpose of this research was the production of microparticles based on whey protein isolate (WPI) and calcium alginate (ALG) containing Calendula officinalis flower extract and their incorporation into films composed of gelatin, WPI, and glycerol. Both swollen and dry microparticles were studied by optical microscopy and their sizes were measured. Water absorption by the microparticles, their loading capacity, and the release profile of flower extract were also characterized. The films were analyzed by mechanical tests (Young's modulus, tensile strength, elongation at break), swelling capacity, contact angle, and moisture content measurements. The presented data showed that the active ingredient was successfully enclosed in spherical microparticles and completely released after 75 min of incubation at 37 °C. The incorporation of the microparticles into polymer films caused a decrease in stiffness and tensile strength, simultaneously increasing the ductility of the samples. Moreover, the films containing microparticles displayed higher swelling ability and moisture content compared to those without them. Hence, the materials prepared in this study with Calendula officinalis flower extract encapsulated into polymeric microspheres can be a starting point for the development of new products intended for skin application; advantages include protection of the extract against external factors and a controlled release profile.

Morroniside delays the progression of non-alcoholic steatohepatitis by promoting AMPK-mediated lipophagy

BackgroundNon-alcoholic steatohepatitis (NASH), the inflammatory subtype in the progression of non-alcoholic fatty liver disease, is becoming a serious burden threatening human health, but no approved medication is available to date. Mononoside is a natural active substance derived from Cornus officinalis and has been confirmed to have great potential in regulating lipid metabolism in our previous studies. However, its effect and mechanism to inhibit the progression of NASH remains unclear. PurposeOur work aimed to explore the action of mononoside in delaying the progression of NASH and its regulatory mechanisms from the perspective of regulating lipophagy. Methods and resultsMale C57BL/6 mice were fed with a high-fat and high-fructose diet for 16 weeks to establish a NASH mouse model. After 8 weeks of high-fat and high-fructose feeding, these mice were administrated with different doses of morroniside. H&E staining, ORO staining, Masson staining, RNA-seq, immunoblotting, and immunofluorescence were performed to determine the effects and molecular mechanisms of morroniside in delaying the progression of NASH. In this study, we found that morroniside is effective in attenuating hepatic lipid metabolism disorders and inflammatory response activation, thereby limiting the progression from simple fatty liver to NASH in high-fat and high-fructose diet-fed mice. Mechanistically, we identified AMPK signaling as the key molecular pathway for the positive efficacy of morroniside by transcriptome sequencing. Our results revealed that morroniside maintained hepatic lipid metabolism homeostasis and inhibited NLRP3 inflammasome activation by promoting AMPKα phosphorylation-mediated lipophagy and fatty acid oxidation. Consistent results were observed in palmitic acid-treated cell models. Of particular note, silencing AMPKα both in vivo and in vitro reversed morroniside-induced lipophagy flux enhancement and NLRP3 inflammasome inhibition, emphasizing the critical role of AMPKα activation in the effect of morroniside in inhibiting NASH progression. ConclusionIn summary, the present study provides strong evidence for the first time that morroniside inhibits NASH progression by promoting AMPK-dependent lipophagy and inhibiting NLRP3 inflammasome activation, suggesting that morroniside is expected to be a potential molecular entity for the development of therapeutic drugs for NASH.

Phenolic profile and evaluation of antimicrobial and anticancer activities of Calendula officinalis L. using exogenous polyamines application

Polyamines (PAs) are active natural substances with multiple amino groups that are essential for numerous physiological and developmental functions in plants. This study aimed to examine the effects of foliar spraying of PAs on profiles of phenolic compounds (PCs), antimicrobial activity against clinical pathogens, and cytotoxic activity of aqueous and methanolic extracts (AEs and MEs) of pot marigold (Calendula officinalis L.) (CoL). Three different quantities of the chemicals putrescine (PUT), spermidine (SPD), and spermine (SPM) were sprayed on the plants during their four or five completely expanded leaf stages.This experiment was carried out over the course of three months, using a randomized complete design with four replications. According to evaluations of various physiochemical characteristics, the treatments significantly increased the amount of glycosylated flavonols. The study also revealed noteworthy differences in the total phenolic acid and flavonoid content. The foliar spraying with 1 mM SPD had the most significant effect compared to other PAs. Additionally, the primary flavonols, including isorhamnetin-3-O-rutinoside (narcissin) and isorhamnetin-3-O-rhamnosylrutinoside (typhaneoside), were observed in the 1 mM SPD treatment. The antimicrobial activity (MIC µg/mL) of CoL AEs and MEs towards the six pathogen strains was significantly enhanced when exogenous application of PAs was introduced. On the other hand, the findings demonstrated that the application of PAs, particularly SPD, led to significant cytotoxic activity against five tumor cell lines in the CoL MEs and AEs. These results indicate that foliar spraying of PAs may have numerous possible uses in the pharmaceutical industry as a result of their influence on antimicrobial and anticancer capacities, as well as phenolic and flavonoid compounds.

Identification and Functional Validation of Two Novel Antioxidant Peptides in Saffron.

Saffron (Crocus sativus L.) is one of the most expensive spices in the world, boasting rich medicinal and edible value. However, the effective development of active natural substances in saffron is still limited. Currently, there is a lack of comprehensive studies on the saffron stigma protein, and the main effect peptides have not been identified. In this study, the total protein composition of saffron stigmas was analyzed, and two main antioxidant peptides (DGGSDYLGK and VDPYFNK) were identified, which showed high antioxidant activity. Then, the stability of two peptides was further evaluated. Furthermore, our results suggested that these two peptides may protect HepG2 cells from H2O2-induced oxidative damage by significantly improving the activity of endogenous antioxidant enzymes and reducing the malondialdehyde (MDA) content. Collectively, we identified two peptides screened from the saffron protein possessing good antioxidant activity and stability, making them promising candidates for use as functional foods, etc., for health promotion. Our findings indicated that proteomic analysis together with peptide identification is a good method for exploitation and utilization of spice plants.

Immunoenhancement effect of cinobufagin on macrophages and the cyclophosphamide-induced immunosuppression mouse model

Cinobufagin (CBG) is a natural active substance. Although its various pharmacological activities have been explored, the immunomodulatory activity of CBG remains unexplored. Therefore, this study aimed to investigate the anti-inflammatory and immunomodulatory activities of CBG ex vivo and in vivo. The immunomodulatory activity of CBG was investigated in RAW 264.7 cells. CBG showed no significant toxicity to cells. Additionally, 0.5–8 μg/mL CBG significantly increased the phagocytosis ability of macrophages and the secretion levels of IL-1β and TNF-α. Thus, it exerted immunomodulatory effects. We established the immunosuppressive model induced by cyclophosphamide (CTX) in mice and studied the immunomodulatory activity of CBG in vivo. The experimental results showed that the intervention of CBG alleviated the CTX-induced weight loss, restored the lymphocyte nuclear cell number, and promoted the secretion and mRNA expression of cytokines IFN-γ, IL-4, IL-6, and IL-12. Moreover, CBG increased the immune organ index, protected the growth of the spleen and thymus, and improved the pathological changes in immunosuppressed mice. Western blot results showed that different concentrations of CBG upregulated the phosphorylation level of PI3K/Akt/mTOR in the spleen of CTX-induced immunosuppressed mice. This suggests that the immunomodulatory effect of CBG may be related to the regulation of PI3K/Akt/mTOR signaling pathway. This study provides a theoretical basis for developing CBG immune enhancers and opens up new ideas for the comprehensive utilization and development of CBG in factories.

An in silico scheme for optimizing the enzymatic acquisition of natural biologically active peptides based on machine learning and virtual digestion

BackgroundAs a potential natural active substance, natural biologically active peptides (NBAPs) are recently attracting increasing attention. The traditional proteolysis methods of obtaining effective NBAPs are considerably vexing, especially since multiple proteases can be used, which blocks the exploration of available NBAPs. Although the development of virtual digesting brings some degree of convenience, the activity of the obtained peptides remains unclear, which would still not allow efficient access to the NBAPs. It is necessary to develop an efficient and accurate strategy for acquiring NBAPs. ResultsA new in silico scheme named SSA-LSTM-VD, which combines a sparrow search algorithm-long short-term memory (SSA-LSTM) deep learning and virtually digested, was presented to optimize the proteolysis acquisition of NBAPs. Therein, SSA-LSTM reached the highest Efficiency value reached 98.00 % compared to traditional machine learning algorithms, and basic LSTM algorithm. SSA-LSTM was trained to predict the activity of peptides in the proteins virtually digested results, obtain the percentage of target active peptide, and select the appropriate protease for the actual experiment. As an application, SSA-LSTM was employed to predict the percentage of neuroprotective peptides in the virtual digested result of walnut protein, and trypsin was ultimately found to possess the highest value (85.29 %). The walnut protein was digested by trypsin (WPTrH) and the peptide sequence obtained was analyzed closely matches the theoretical neuroprotective peptide. More importantly, the neuroprotective effects of WPTrH had been demonstrated in nerve damage mouse models. SignificanceThe proposed SSA-LSTM-VD in this paper makes the acquisition of NBAPs efficient and accurate. The approach combines deep learning and virtually digested skillfully. Utilizing the SSA-LSTM-VD based strategy holds promise for discovering and developing peptides with neuroprotective properties or other desired biological activities.

Protein‐based active films: Raw materials, functions, and food applications

AbstractBiopolymer packaging materials are an emerging trend in food packaging due to their degradability, nontoxicity, low cost, and low environmental stress; moreover, some properties of biopolymer packaging are better than those of traditional packaging. Proteins are a type of natural biopolymer packaging film matrix, and enhancing the packaging properties of proteins has been a focus of research. Preparing protein‐active packaging films by adding natural active substances with antimicrobial and antioxidant properties and nanoparticles to protein‐based films to provide more significant antimicrobial, antioxidant, and UV‐blocking effects is essential in food packaging and demonstrates the potential of using proteins in active food packaging applications. In recent years, the origin of natural actives, their mechanism of action, and their release from active packaging films have attracted much attention. In this review, we provide a comprehensive overview of protein film matrices for active packaging, natural antimicrobial agents, and natural antioxidants and discuss the potential of such active films in the packaging field. The sources of natural antimicrobial active substances and natural antioxidant active substances in packaging materials, their mechanisms of action, and their effects after being used to modify protein active films are summarized. The biorelease functions of protein active films with antimicrobial and antioxidant effects and their applications for various types of food are highlighted to understand the current effects of protein active films in food packaging.

Biyang floral mushroom-derived exosome-like nanovesicles: characterization, absorption stability and ionizing radiation protection.

Diet-derived exosome-like nanovesicles are a class of natural active substances that have similar structures and functions to mammalian exosomes. Biyang floral mushrooms and their active extracts have been found to possess radioprotective effects and to deeply explore their novel active substances, the radioprotective effects of Biyang floral mushroom-derived exosome-like nanovesicles (BFMELNs) were investigated in this study. Results showed that these surface-negatively charged vesicles possessed an ideal size and good stability against environmental changes such as temperature and gastrointestinal digestion. Furthermore, BFMELNs could effectively be taken up by HL-7702 cells and Caco-2 cells through cellular phagocytosis mediated by clathrin and dynein. Emphatically, BFMELNs with an exosome-like morphology contained RNA, proteins, lipids, polyphenols and flavonoids to exert good antioxidant and radioprotective effects in vitro. Meanwhile, BFMELNs also exhibited good radioprotective effects by restoring peripheral blood indexes, mitigating damage to organs, and regulating the redox state in mice. Collectively, BFMELNs showed promise as novel and natural radioprotective nano-agents for preventing IR-induced oxidative stress damage.

Phytosomes: A Novel approach for improving the efficacy of Herbal Extracts

A phytosome is defined as a combination of a phospholipid and a natural active substance. One of the lipid- based vesicular delivery methods is the phytosome, which can be used to encapsulate drugs and nutraceuticals derived from plants polyphenolic chemicals. Phytosomes are said to boost the absorption of traditional herbal remedies topically and orally. Phytosomes aid in increasing the solubility and bioavailability of polyphenolic substances through the gastrointestinal tract. Phytosomes preparation is simple to make and can be scaled up for business use easily. This article elaborates the concept of phytosome with detailed information regarding its structure, properties, applications preparation, and evaluation methods.