Isolation and microbial transformation of tea sapogenin from seed pomace of Camellia oleifera with anti-inflammatory effects.

In the current study, tea saponin, identified as the primary bioactive constituent in seed pomace of Camellia oleifera Abel., was meticulously extracted and hydrolyzed to yield five known sapogenins: 16-O-tiglogycamelliagnin B (a), camelliagnin A (b), 16-O-angeloybarringtogenol C (c), theasapogenol E (d), theasapogenol F (e). Subsequent biotransformation of compound a facilitated the isolation of six novel metabolites (a1-a6). The anti-inflammatory potential of these compounds was assessed using pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns molecules (DAMPs)-mediated cellular inflammation models. Notably, compounds b and a2 demonstrated significant inhibitory effects on both lipopolysaccharide (LPS) and high-mobility group box 1 (HMGB1)-induced inflammation, surpassing the efficacy of the standard anti-inflammatory agent, carbenoxolone. Conversely, compounds d, a3, and a6 selectivity targeted endogenous HMGB1-induced inflammation, showcasing a pronounced specificity. These results underscore the therapeutic promise of C. oleifera seed pomace-derived compounds as potent agents for the management of inflammatory diseases triggered by infections and tissue damage.

Novel MeON-glycosides of ursolic acid: Synthesis, antitumor evaluation, and mechanism studies.

Ursolic acid (UA) is a pentacyclic triterpenoid widely found in in medicinal plants, edible plants, fruits, and flowers. The great interest in this bioactive compound is related to the positive effects in human health. However, its limited solubility, moderate biological activity and poor bioavailability limit the potential and further applications of UA. Here, we explored the efficacy of MeON-Glycosides of UA in inhibiting tumor cell proliferation. A number of compounds showed significant antitumor activity against tested five cancer cell lines. Among them, compound 2a exhibited the most potent activity against HepG2 cells with IC50 values of 3.1 ± 0.5 µM. Especially, compound 2a could induce HepG2 cells apoptosis and reduce mitochondrial membrane potential. Western blot analysis showed that compound 2a up-regulated Bax, cleaved caspase-3/9, cleaved PARP levels and down-regulated Bcl-2 level of HepG2 cells. These results indicated that compound 2a could obviously induce the apoptosis of HepG2 cells. At the same time, compound 2a significantly decreased the expression of p-AKT and p-mTOR, which indicated that compound 2a might exert its cytotoxic effect by targeting PI3K/AKT/mTOR signaling pathway. Moreover, the in silico ADME predictions showed that compound 2a has improved water solubility and other properties. Thus, compound 2a may be a promising antitumor candidate, which may be potentially used to prevent or treat cancers.

Integrating Bioinformatics and Network Pharmacology to Explore the Therapeutic Target and Molecular Mechanisms of Schisandrin on Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is currently the leading cause of sudden death in adolescent athletes. Schisandrin is a quality marker of the traditional Chinese medicine Schisandra chinensis, which has an excellent therapeutic effect on HCM, but its pharmacological mechanism remains unclear. OBJECTIVE: This study aimed to explore the potential and provide scientific evidence for schisandrin as a lead compound against hypertrophic cardiomyopathy. METHODS: The drug-like properties of schisandrin were predicted using the SwissADME website. Then, the PharmMapper database was used to predict potential drug targets and match gene names in the Uniprot database. HCM targets were collected from NCBI, OMIM, and Genecards databases and intersected with drug targets. The intersection targets were imported into the STRING database for PPI analysis, and core targets were identified. KEGG and GO enrichment analysis was performed on the core targets through the DAVID database, and all network maps were imported into Cytoscape software for visualization optimization. HCM-related datasets were downloaded from the GEO database to analyze core targets and screen differentially expressed target genes for molecular docking. RESULTS: After the PPI network analysis of the intersection targets of drugs and diseases, 12 core targets were screened out. The KEGG analysis results showed that they were mainly involved in Rap1, TNF, FoxO, PI3K-Akt, and other signaling pathways. After differential analysis, PPARG, EGFR, and MMP3 targets were also screened. The molecular docking results showed that schisandrin was well bound to the protein backbone of each target. CONCLUSION: This study used network pharmacology combined with differential expression and molecular docking to predict that schisandrin may treat HCM by acting on PPARG, EGFR, and MMP3 targets, and the regulatory process may involve signaling pathways, such as Rap1, TNF, FoxO, and PI3K-Akt, which may provide a valuable reference for subsequent studies.

Gene-Modified Stem Cells for Spinal Cord Injury: a Promising Better Alternative Therapy.

Stem cell therapy holds great promise for the treatment of spinal cord injury (SCI), which can reverse neurodegeneration and promote tissue regeneration via its pluripotency and ability to secrete neurotrophic factors. Although various stem cell-based approaches have shown certain therapeutic effects when applied to the treatment of SCI, their clinical efficacies have been disappointing. Thus, it is an urgent need to further enhance the neurological benefits of stem cells through bioengineering strategies including genetic engineering. In this review, we summarize the progress of stem cell therapy for SCI and the prospect of genetically modified stem cells, focusing on the genome editing tools and functional molecules involved in SCI repair, trying to provide a deeper understanding of genetically modified stem cell therapy and more applicable clinical strategies for SCI repair.

Derivatization of Soyasapogenol A through Microbial Transformation for Potential Anti-inflammatory Food Supplements.

For the optimum use of soyasaponins isolated from soybean cake and to explore the potential anti-inflammatory agents from pentacyclic triterpenes as natural food supplements, microbial transformation of soyasapogenol A was carried out. Four strains of microbes, including Bacillus megaterium CGMCC 1.1741, Penicillium griseofulvum CICC 40293, Bacillus subtilis ATCC 6633, and Streptomyces griseus ATCC 13273, showed robust catalytic capacity to the substrate. Preparative biotransformation and column chromatographic purification led to the isolation of 10 novel and 1 reported metabolites. The structure elucidation was performed using 1D/2D NMR and HR-ESI-MS analytical method. Several novel tailoring reactions, such as allyl oxidation, C-C double bond rearrangement, hydroxylation, dehydrogenation, and glycosylation, were observed in the biotransformation. In the follow-up bioassay, most of the metabolites exhibited low cytotoxicity and potent inhibitory activity against the production of nitric oxide (NO) in RAW 264.7 cells stimulated by lipopolysaccharide. Especially compound 6 (3-oxo-11α,21ß,22ß,24-tetrahydroxy-olean-12-ene) showed comparable activity to the positive control of quercetin with an IC50 value of 16.70 µM. These findings provided an experimental approach to achieve the derivatization of natural aglycons in soybeans through microbial transformation for developing potent anti-inflammatory food supplements.

Induced pluripotent stem cell technology for spinal cord injury: a promising alternative therapy.

Spinal cord injury has long been a prominent challenge in the trauma repair process. Spinal cord injury is a research hotspot by virtue of its difficulty to treat and its escalating morbidity. Furthermore, spinal cord injury has a long period of disease progression and leads to complications that exert a lot of mental and economic pressure on patients. There are currently a large number of therapeutic strategies for treating spinal cord injury, which range from pharmacological and surgical methods to cell therapy and rehabilitation training. All of these strategies have positive effects in the course of spinal cord injury treatment. This review mainly discusses the problems regarding stem cell therapy for spinal cord injury, including the characteristics and action modes of all relevant cell types. Induced pluripotent stem cells, which represent a special kind of stem cell population, have gained impetus in cell therapy development because of a range of advantages. Induced pluripotent stem cells can be developed into the precursor cells of each neural cell type at the site of spinal cord injury, and have great potential for application in spinal cord injury therapy.

Biotransformation of Erythrodiol for New Food Supplements with Anti-Inflammatory Properties.

Erythrodiol, a typical pentacyclic triterpenic diol in olive oil and its byproduct, olive pomace, frequently appears in food additives for the prevention of cardiovascular diseases because of its antioxidation, anti-inflammatory, and antitumor activities. To develop new derivatives of erythrodiol (1), preparative biotransformations were investigated through Streptomyces griseus ATCC 13273, Penicilium griseofulvum CICC 40293, and Bacillus subtilis ATCC 6633, and ten new (1a-1j) and one known metabolites were isolated. Their structures were elucidated by high resolution electrospray ionization mass spectrometry (HR-ESI-MS) and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy. Furthermore, relative to 1, most metabolites exhibited lower toxicity and more potent inhibitory activities against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In particular, the glycosylated metabolite 1k showed a dramatically increased inhibitory effect with an IC50 value of 2.40 µM, which is even lower than that of quercetin. Thus, biotransformation of erythrodiol is a viable strategy for discovering new triterpenes as food supplements with anti-inflammatory properties.

Is phosphorus a limiting factor to regulate the growth of phytoplankton in Daya Bay, northern South China Sea: a mesocosm experiment.

Previous field investigations implied a potential phosphorus (P)-limitation on the growth of phytoplankton in Daya Bay, a mesotrophic bay in the northern South China Sea. Using a total of 15 mesocosms (3 × 3 × 1.5 m, with ~10.8 m3 natural seawater containing phytoplankton assemblages for each), we found P-enrichment caused no obvious effect on phytoplankton (Chl a) growth across 8-day's cultivation in neither winter nor summer, while nitrogen (N)-enrichment greatly increased Chl a in both seasons. N plus P-enrichment further increased Chl a content. The N- or N plus P-enrichments increased the allocation of nano-Chl a but decreased micro-Chl a in most cases, with no obvious effect by P-alone. Coincided with nutrients effect on Chl a content, N- or N plus P-enrichments significantly enhanced the maximum photochemical quantum yield of Photosystem II (FV/FM) and maximum relative electron transport rate (rETRmax), but declined the non-photochemical quenching (NPQ), as well as the threshold for light saturation of electron transport (EK); again, P-enrichment had no significant effect. Moreover, the absorption cross section for PSII photochemistry (σPSII) and electron transport efficiency (α) increased due to N- or N plus P-enrichments, indicating the increased nutrients enhance the light utilization efficiency through promoting PSII light harvesting ability, and thus to enhance phytoplankton growth. Our findings indicate that N- or N plus P-enrichments rigorously fuel phytoplankton blooms regardless of N:P ratios, making a note of caution on the expected P-deficiency or P-limitation on the basis of Redfield N:P ratios in Daya Bay.

Evidence of iron cyanides as supplementary nitrogen source to rice seedlings.

The effect of iron cyanides on activities of nitrate reductase (NR) and glutamine synthetase (GS) of plants was investigated. Young rice seedlings (Oryza sativa L. cv. XZX 45) were grown in the nutrient solutions containing KNO(3) or NH(4)Cl and treated with ferro-cyanide [K(4)Fe(CN)(6)] or ferri-cyanide [K(3)Fe(CN)(6)]. Total cyanide and free cyanide in solutions and in plant materials were analyzed. Activities of NR and GS in different parts of plants were assayed in vivo. Results indicated that all rice seedlings exposed to either ferro- or ferri-cyanide showed positive growth. The phyto-assimilation rates of both iron cyanide species by rice seedlings were positively correlated to the doses supplied. Seedlings grown on NO(3)(-) showed significantly higher assimilatory potential for both ferro- and ferri-cyanide than those on NH(4)(+). Rice seedlings grown on NH(4)(+)-containing nutrient solution accumulated more cyanide in plant materials, majority being in roots rather than shoots, than these grown on NO(3)(-)-containing nutrient solution, suggesting that the presence of ammonium (NH(4)(+)) in the nutrient solution caused a negative impact on botanical assimilation of both iron cyanides. Sensitivity of NR and GS in rice seedlings exposed to ferro- and ferri-cyanide was identical, where conspicuous effects were only observed at the highest concentration supplied. The evidence offered here suggests that both iron cyanides can be a supplementary source of nitrogen to plant nutrition.