Fused Azulenyl Squaraine Derivatives Improve Phototheranostics in the Second Near-Infrared Window by Concentrating Excited State Energy on Non-Radiative Decay Pathways.

The second near-infrared (NIR-II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR-II light. However, traditional regimens lacking effective NIR-II absorption and uncontrollable excited-state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano-agent (PS-1 NPs) based on azulenyl squaraine derivatives with a strong NIR-II absorption band centered at 1092 nm is reported, allowing almost all absorbed excitation energy to dissipate through non-radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS-1 NPs. Even in the 5 mm deep-seated tumor model, PS-1 NPs demonstrated a satisfactory anti-tumor effect in photoacoustic imaging-guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS-1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR-II theranostic agents in oral medicine.

Lobetyolin, a Q-marker isolated from Radix Platycodi, exerts protective effects on cisplatin-induced cytotoxicity in HEK293 cells.

This study investigated the protective effect of lobetyolin (LBT), a Q-marker isolated from the roots of Platycodon grandiflorum (Radix Platycodi), against cisplatin-induced cytotoxicity in human embryonic kidney (HEK293) cells. Results showed that LBT at 20 µM significantly prevented cisplatin-induced cytotoxicity by improving the viability of HEK293 cells, decreasing levels of MDA, and decreasing GSH content triggered by cisplatin. It also suppressed reactive oxygen species (ROS) levels. Molecular docking analysis revealed a strong binding affinity between LBT and the NF-κB protein, with a docking fraction of - 6.5 kcal/mol. These results provide compelling evidence suggesting a potential link between the visualization analysis of LBT and its protective mechanism, specifically implicating the NF-κB signaling pathway. LBT also reduced the expression level of tumor necrosis factor-alpha (TNF-α), phosphorylation NF-κB and IκBα in HEK293 cells which were increased by cisplatin exposure, leading to inhibition of inflammation. Furthermore, western blotting showed that LBT antagonized the up-regulation of Bax, cleaved caspase 3, 8, and 9 expression and inhibited the MAPK signaling pathway by down-regulating phosphorylation JNK, ERK, and p38, partially ameliorating cisplatin-induced cytotoxicity in HEK293 cells. Therefore, these results indicate that LBT has potentially protected renal function by inhibiting inflammation and apoptosis.

Platycodin D inhibits HFD/STZ-induced diabetic nephropathy via inflammatory and apoptotic signaling pathways in C57BL/6 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried root of Platycodon grandiflorum (Jacq.) A.DC. (PG) is a traditional herb used in Asian countries and is widely used in formulas for the treatment of diabetes. Platycodin D (PD) is one of the most important components of PG. AIM OF THE STUDY: This study aimed to investigate the improvement effects and regulatory mechanisms of PD on kidney injury in a high-fat diet (HFD) combined with streptozotocin (STZ)-induced diabetic nephropathy (DN). MATERIALS AND METHODS: Model mice were treated with oral gavage of the PD (2.5, 5 mg/kg) for 8 weeks. Determination of serum lipid and renal function-related indexes creatinine (CRE), and blood urea nitrogen (BUN) levels in mice, and histopathological section analysis of kidney. Molecular docking and molecular dynamics were utilized to study the binding ability of PD to target NF-κB and apoptosis signaling pathway-related proteins. Moreover, Western blot was used to test the expressions of NF-κB and apoptosis-related proteins. Vitro experiments were performed to validate the related mechanisms using RAW264.7 cells and HK2 cells cultured by high glucose. RESULTS: In vivo experiments, the administration of PD (2.5 and 5.0 mg/kg) reduced fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR) levels in DN mice, while lipid levels and renal function were significantly improved. Furthermore, PD significantly inhibited the development of DN in the model mice by regulating NF-κB and apoptotic signaling pathways, reduced the abnormal elevation of serum inflammatory factors TNF-α and IL-1ß, and repaired renal cell apoptosis. In vitro experiments, NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (PDTC) was used to confirm that PD can alleviate high glucose-induced inflammation in RAW264.7 cells and inhibit the release of inflammatory factors. And in HK2 cell experiments, it was verified that PD can inhibit ROS generation, reduce the loss of JC-1 and suppress HK2 cell injury by regulating NF-κB and apoptotic pathways. CONCLUSIONS: These data suggested that PD has the potential to prevent and treat DN and is a promising natural nephroprotective agent.

Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network Pharmacology.

In this study, we evaluated the ameliorative effect and molecular mechanism of red ginseng (Panax ginseng C.A. Meyer) extract (RGE) on D-galactose (D-gal)-induced premature ovarian failure (POF) using network pharmacology analysis. Ginsenosides are important active ingredients in ginseng, which also contains some sugar and amino acid derivatives. We aimed to determine the key proteins through which RGE regulates POF. In this work, we retrieved and screened for active ingredients in ginseng and the corresponding POF disease targets in multiple databases. A PPI network of genes was constructed in the STRING database and core targets were screened using topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in R software. Finally, molecular docking was conducted to validate the results. Female ICR mice were used to establish a POF mouse model for in vivo experiments. Serum levels of relevant estrogens were determined using ELISA and expression levels of relevant proteins in ovarian tissues were detected using immunofluorescence and western blot analysis. Network pharmacology analysis predicted that PI3K, Akt, Bax, Bcl-2, p16, and other proteins were highly correlated with POF and RGE. The results clearly showed that RGE could increase estradiol (E2) and lower follicle-stimulating hormone (FSH) levels in D-gal-fed mice. RGE restored the expression levels of related proteins by reducing Nrf2-mediated oxidative stress, PI3K/Akt-mediated apoptosis, and senescence signaling pathways. Overall, RGE has the potential to prevent and treat POF and is likely to be a promising natural protector of the ovaries.

Platycodin D stimulates AMPK activity to inhibit the neurodegeneration caused by reactive oxygen species-induced inflammation and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) was considered to be a neurodegenerative disease that caused cognitive impairment. Reactive Oxidative stress (ROS) was considered to be one of a major cause of the onset and progression of AD. Platycodin D (PD), a representative saponin from Platycodon grandiflorum, has conspicuous antioxidant activity. However, whether PD could protect nerve cell against oxidative injury remains unknown. AIM OF STUDY: This study investigated the regulatory effects of PD on neurodegeneration caused by ROS. To determine whether PD could play its own antioxidant role in neuronal protection. MATERIALS AND METHODS: First, PD(2.5, 5 mg/kg) ameliorated the memory impairment induced by AlCl3 (100 mg/kg) combined with D-galactose (D-Gal) (200 mg/kg) in mice, using the radial arm maze (RAM) test, and neuronal apoptosis in the hippocampus was evaluated by hematoxylin and eosin staining (HE). Next, the effects of PD (0.5, 1, and 2 µM) on okadaic-acid (OA) (40 nM) -induced apoptosis and inflammation of HT22 cells were investigated. Mitochondrial ROS production was measured by fluorescence staining. The potential signaling pathways were identified through Gene Ontology enrichment analysis. The role of PD in regulating AMP-activated protein kinase (AMPK) was assessed using siRNA silencing of genes and an ROS inhibitor. RESULTS: In vivo, PD improved memory in mice, and recovered the morphological changes of brain tissue and nissl bodies. In vitro experiment, PD increased cell viability (p < 0.01; p < 0.05;p < 0.001), decreased apoptosis (p < 0.01), reduced excessive ROS and MDA, rised SOD and CAT content(p < 0.01; p < 0.05). Morover, it can block the inflammatory response caused by ROS. Be important, PD strengthen antioxidant ability by elevating AMPK activation both in vivo and in vitro. Furthermore, molecular docking suggested a good likelihood of PD-AMPK binding. CONCLUSION: AMPK activity is vital for the neuroprotective effect of PD, suggesting that PD may be a potential pharmaceutical agent to treat ROS-induced neurodegeneration.

Review on potential effects of traditional Chinese medicine on glaucoma.

ETHNIC PHARMACOLOGICAL RELEVANCE: Glaucoma is the second most common blindness in the world, which seriously affects the life quality of patients. Traditional Chinese Medicines (TCM), are important plant materials, widely used for ocular disease all over the world. With the help of modern ophthalmic detection technology, TCM has gradually become an important content in the field of ophthalmology, characterized by more targets and lower toxicity. AIM OF THIS REVIEW: This review presents an overview of the pathogenesis of glaucoma in both modern and traditional medicines, and summarizes the therapeutic effect of TCM on glaucoma including their formula, crude drugs and active components, and also the application of acupuncture. METHODS: A collection and collation of relevant scientific articles from different scientific databases was performed regarding TCM and its application on glaucoma. The therapeutic effects of TCM were summarized and analyzed according to the existing experimental and clinical researches, while the GSE26299 database were employed to screen bioinformatics analysis of glaucoma based on the GEO database chip. RESULTS: There were many positive signs showing that TCM could increase the survival rate of retinal ganglion cells, which may be related to its regulation of microcirculation, oxidative stress, and the immune system. Hence, TCM plays an active role in treating glaucoma. In addition, the bioinformatics analysis predicted that the pathogenesis of glaucoma might be related to p53, MAPK, NF-κB signal, as well as other pathways by KEGG analysis, and the results from bioinformatics analysis predicted that PIK3R6, FGF1, and TYRP1 etc. CONCLUSION: TCM exerts definite effects on preventing and treating ocular disease. It could alleviate and treat glaucoma in various ways. The differentiation syndrome should thus be taken as the basis to propose appropriate treatment options of TCM making their application on glaucoma more popular.

Protective Effect of Ginsenosides from Stems and Leaves of Panax ginseng against Scopolamine-Induced Memory Damage via Multiple Molecular Mechanisms.

Although growing evidence has shown that ginsenosides from stems and leaves of Panax ginseng (GSLS) exercise a protective impact on the central nervous system, in the model of memory damage induced by scopolamine, it is still rarely reported. Thus, the mechanism of action needs to be further explored. This study was to investigate the effect of GSLS on scopolamine (SCOP)-induced memory damage and the underlying mechanism. Male ICR mice were treated with SCOP (3 mg/kg) for 7 days, with or without GSLS (75 and 150 mg/kg) treatment for 14 days. After GSLS treatment, the memory damage induced by SCOP was significantly ameliorated as shown by the improvement of cholinergic function (AChE and ChAT), brain tissue hippocampus morphology (H&E staining), and oxidative stress (MDA, GSH, and NO). Meanwhile, immunohistochemical assay suggested that GSLS increased the expression of brain-derived neurotrophic factor (BDNF) and Tyrosine Kinase receptor B (TrkB). Further mechanism research indicated that GSLS inhibited the Tau hyperphosphorylation and cell apoptosis by regulating the PI3K/AKT pathway and inhibited neuroinflammation by regulating the NF-κB pathway, thereby exerting a cognitive impairment improvement effect. This work suggested that GSLS could protect against SCOP-induced memory defects possibly through inhibiting oxidative stress, inhibiting neuroinflammation and cell apoptosis.

High-resolution profiles of dissolved reactive phosphorus in overlying water and porewater of Lake Taihu, China.

The diffusive gradients in thin films (DGT) technique was applied to obtain high spatial resolution of dissolved reactive phosphorus (DRP) concentrations in overlying water and sediment porewater in Lake Taihu. A strong positive correlation between total phosphorus (TP) in sediments and DRP concentrations using DGT was found in both of the sampled lake regions. For stations ZSW and DPG, which have high TP background values in sediments, DRP concentrations in overlying water and porewater were much higher than those at stations MLW, DPG, and HX. Also, a high potential for P release at the sediment-water interface was revealed at stations ZSW and DPG due to a significant concentration gradient between overlying water and porewater. In sediment cores from stations ZSW and DPG, DRP porewater concentration profiles using DGT with three diffusive gel thicknesses displayed a similar trend, increasing down to -2 cm or -4 cm, then decreasing down to -8 cm, and then becoming relatively stable in deeper layers. High-resolution profiles of DRP were related to dissolved oxygen concentrations and organic matter concentrations in different sediment layers at stations ZSW and DPG. For most sediment with low TP concentrations at stations MLW, DPG, and HX, DRP concentrations could not be determined at and near the sediment-water interface, then increased gradually down to -8 cm or -10 cm, and remained stable. At stations MLW, DPG, and HX, most DRPDGT (DRP concentrations measured by DGT) values were 10-30 % of the DRP concentrations in porewater, indicating a partial resupply of the sediments to porewater.

A 60-year sedimentary record of natural and anthropogenic impacts on Lake Chenghai, China.

Recent sediments from Lake Chenghai, China, were investigated at high temporal resolution to trace both natural and anthropogenic effects on the lake using total organic carbon (TOC), total nitrogen (TN), total phosphorus (TP), organic phosphorus (Po), inorganic phosphorus (Pi) and organic carbon and nitrogen stable isotopes (delta13Corg and delta15N) in a 137Cs-dated sediment core. The results indicated that the sedimentary record covers the last 60 years, during which the lake had undergone apparent changes in nutrient sources and productivity in response to nutrient loading. Prior to the late 1980s, the nutrient contents in sediments mainly originated from algae and lake productivity was relatively stable. Since the late 1980s, increasing TOC, TN and TP concentrations together with the change of delta13Corg and delta15N suggested anthropogenic perturbations in nutrient loading and lake productivity. Endogenic nutrients derived from algae and anthropogenic inputs were two important sources of sedimentary nutrients. The anthropogenic nutrients mainly originated from the discharge of industrial wastewater and artificial cultivation of Spirulina after the middle 1980s, and domestic wastewater discharged from Yongsheng County since 1993.

A 100-year sedimentary record of natural and anthropogenic impacts on a shallow eutrophic lake, Lake Chaohu, China.

In this study, the sediment profiles of total organic carbon, total nitrogen, C/N ratios, total phosphorus, N/P ratios, C/P ratios, particle sizes, and stable carbon and nitrogen isotopes (δ(13)C and δ(15)N) were used to investigate natural and anthropogenic impacts on Lake Chaohu over the past 100 years. Before 1960, Lake Chaohu experienced low productivity and a relatively steady and low nutrient input. The increasing concentration and fluxes of total organic carbon, total nitrogen, total phosphorus, together with changes in the δ(13)C and δ(15)N of organic material in the sediment cores, suggested that the anthropogenic effects on trophic status first started because of an increase in nutrient input caused by a population increase in the drainage area. With the construction of the Chaohu Dam, an increase in the utilization of fertilizer and the population growth which occurred since 1960, stable depositional conditions and increasing nutrient input resulted in a dominantly algae-derived organic matter source and high productivity. Nutrient input increased most significantly around 1980 following the rapidly growing population, with concomitant urbanization, industrial and agricultural development. This study also revealed that the concentration and distribution of nutrients varied between different areas of sediment within Lake Chaohu because of the influence of different drainage basins and pollution sources.

Phosphorus fractionation in different trophic sediments of lakes from different regions, China.

The characteristics of organic phosphorus (P(o)) fractions in the sediments of nine lakes from the middle and lower reaches of the Yangtze River region, Yungui Plateau, Qinghai-Tibet Plateau, Northeast China Region, and Mongolia-Xinjiang Plateau, China were investigated and the differences of the different lakes on P fractionation was discussed. The results indicated that organic matter (OM) showed significant positive correlations with P(o) in sediment samples, and the rank order of the P(o) fractions was: residual P(o) > HCl-P(o) > fulvic acid-P(o) > humic acid-P(o) > NaHCO(3)-P(o) with mean relative proportions 7.4 : 3.4 : 2.4 : 1.7 : 1.0. The labile and moderately labile P(o) were the main fractions in the sediments for shallow eutrophic lakes except for Lake Qilu, however, nonlabile P(o) was dominant in the sediments from deep lakes. Labile P(o) was significantly correlated with total phosphorus (TP), inorganic phosphorus (P(i)), P(o), NaHCO(3)-P(i), HCl-P(i) and NaOH-P(i), and the nonlabile P(o) was significantly and positively related to OM, TP, P(o) and NaOH-P(i).