Hydroxysafflor yellow A ameliorates alcohol-induced liver injury through PI3K/Akt and STAT3/NF-κB signaling pathways.

BACKGROUND: Alcohol-associated liver disease (ALD) is a prevalent liver ailment. It has escalated into a significant public health issue, imposing substantial burdens on medical, economic, and social domains. Currently, oxidative stress, inflammation, and apoptosis are recognized as crucial culprits in improving ALD. Consequently, mitigating these issues has emerged as a promising avenue for enhancing ALD. Hydroxysafflor yellow A (HSYA) is the main ingredient in safflower, showing excellent antioxidative stress, anti-inflammatory, and anti-apoptosis traits. However, there are limited investigations into the mechanisms by which HSYA ameliorates ALD PURPOSE: We investigated whether HSYA, a significant constituent of Asteraceae safflower, exerts antioxidant stress and attenuates inflammation and anti-apoptotic effects through PI3K/Akt and STAT3/NF-κB pathways, thereby ameliorating ALD METHODS: We established two experimental models: an ethanol-induced liver damage mouse model in vivo and a HepG2 cell alcohol injury model in vitro RESULTS: The results demonstrated that HSYA effectively ameliorated liver tissue damage, reduced levels of ALT, AST, LDL-C, TG, TC, and MDA, enhanced HDL-C levels, SOD and GSH activities, reduced ROS accumulation in cells, and activated the Nrf2 pathway, a transcription factor involved in antioxidant defense. By regulating the PI3K/Akt and STAT3/NF-κB pathways, HSYA exhibits notable antioxidative stress, anti-inflammatory, and anti-apoptotic effects, effectively impeding ALD's advancement. To further confirm the regulatory effect of HSYA on PI3K/Akt and downstream signaling pathways, the PI3K activator 740 Y-P was used and was found to reverse the downregulation of PI3K by HSYA CONCLUSION: This study supports the effectiveness of HSYA in reducing ALD by regulating the PI3K/Akt and STAT3/NF-κB pathways, indicating its potential medicinal value.

Anti-oxidative stress treatment and current clinical trials.

Oxidative stress disturbs the balance between the production of reactive oxygen species (ROS) and the detoxification biological process. It plays an important role in the development and progression of many chronic diseases. Upon exposure to oxidative stress or the inducers of ROS, the cellular nucleus undergoes some biological processes via different signaling pathways, such as stress adaption through the forkhead box O signaling pathway, inflammatory response through the IκB kinase/nuclear factor-κB signaling pathway, hypoxic response via the hypoxia-inducible factor/prolyl hydroxylase domain proteins pathway, DNA repair or apoptosis through the p53 signaling pathway, and antioxidant response through the Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 signaling pathway. These processes are involved in many diseases. Therefore, oxidative stress has gained more attraction as a targeting process for disease treatment. Meanwhile, anti-oxidative stress agents have been widely explored in pre-clinical trials. However, only limited clinical trials are performed to evaluate the efficacy of anti-oxidative stress agents or antioxidants in diseases. In this letter, we further discuss the current clinical trials related to anti-oxidative stress treatment in different diseases. More pre-clinical studies and clinical trials are expected to use anti-oxidative stress strategies as disease treatment or dietary supplementation to improve disease treatment outcomes.

Microbial dysbiosis and the aging process: a review on the potential age-deceleration role of Lactiplantibacillus plantarum.

Gut microbiota dysbiosis has been a serious risk factor for several gastric and systemic diseases. Recently, gut microbiota's role in aging was discussed. Available preclinical evidence suggests that the probiotic bacteria Lactiplantibacillus plantarums (LP) may influence the aging process via modulation of the gut microbiota. The present review summarized compelling evidence of LP's potential effect on aging hallmarks such as oxidative stress, inflammation, DNA methylation, and mitochondrial dysfunction. LP gavage modulates gut microbiota and improves overall endurance in aging animal models. LP cell constituents exert considerable antioxidant potential which may reduce ROS levels directly. In addition, restored gut microbiota facilitate a healthy intestinal milieu and accelerate multi-channel communication via signaling factors such as SCFA and GABA. Signaling factors further activate specific transcription factor Nrf2 in order to reduce oxidative damage. Nrf2 regulates cellular defense systems involving anti-inflammatory cytokines, MMPs, and protective enzymes against MAPKs. We concluded that LP supplementation may be an effective approach to managing aging and associated health risks.

α-Mangostin suppresses ethanol-induced gastric ulceration by regulating the Nrf2/HO-1 and NF-κB/NLRP3/caspase-1 signaling pathways and gut microbiota.

α-Mangostin is a natural xanthone derivative isolated from Camellia atrophy (CA), commonly known as Lichuan black tea (LBT). The present study investigated the ameliorating effect and mechanism of α-mangostin on alcoholic gastric ulcers (GU) in rats. In vivo, α-mangostin relieved pathological symptoms. Moreover, α-mangostin regulated the activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) and nuclear factor κB (NF-κB)/NLR family pyrin domain containing 3 (NLRP3)/caspase-1 pathways. Reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were significantly decreased and IL-10 were increased, the microtubule-associated protein light chain 3 (LC3)-II/LC3-I ratio was increased, p62 protein expression was decreased, and inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression was down-regulated. The relevant mechanisms were validated using GSE-1 and RAW264.7 cells in an in vitro model. Furthermore, α-mangostin increased Ligilactobacillus and Muribaculum abundance as well as propionic acid and butyric acid contents. Therefore, α-mangostin possesses antioxidant and anti-inflammatory properties, and remodels intestinal flora dysbiosis through mechanisms that may involve regulation of the Nrf2/HO-1 pathway and NF-κB/NLRP3/caspase-1 pathway. It also increases propionic acid and butyric acid contents. This study provides novel evidence regarding the use of α-mangostin for treating GU.

Traditional Scraping (Gua Sha) Combined with Copper-Curcumin Nanoparticle Oleogel for Accurate and Multi-Effective Therapy of Androgenic Alopecia.

Androgenetic alopecia (AGA) is a prevalent systemic disease caused by diverse factors, for which effective treatments are currently limited. Herein, the oleogel (OG) containing copper-curcumin (CuR) nanoparticles is developed, designated as CuRG, which is also combined with traditional naturopathic scraping (Gua Sha, SCR) as a multifunctional therapy for AGA. With the assistance of lipophilic OG and SCR, CuR can efficaciously penetrate the epidermal and dermal regions where most hair follicles (HFs) reside, thereby releasing curcumin (CR) and copper ions (Cu2+) subcutaneously to facilitate hair regeneration. Concomitantly, the mechanical stimulation induced by SCR promotes the formation of new blood vessels, which is conducive to reshaping the microenvironment of HFs. This study validates that the combination of CuRG and SCR is capable of systematically interfering with different pathological processes, ranging from improvement of perifollicular microenvironment (oxidative stress and insufficient vascularization), regulation of inflammatory responses to degradation of androgen receptor, thus potentiating hair growth. Compared with minoxidil, a widely used clinical drug for AGA therapy, the designed synergistic system displays augmented hair regeneration in the AGA mouse model.

Pharmacological properties of Polygonatum and its active ingredients for the prevention and treatment of cardiovascular diseases.

Despite continued advances in prevention and treatment strategies, cardiovascular diseases (CVDs) remain the leading cause of death worldwide, and more effective therapeutic methods are urgently needed. Polygonatum is a traditional Chinese herbal medicine with a variety of pharmacological applications and biological activities, such as antioxidant activity, anti-inflammation, antibacterial effect, immune-enhancing effect, glucose regulation, lipid-lowering and anti-atherosclerotic effects, treatment of diabetes and anticancer effect. There has also been more and more evidence to support the cardioprotective effect of Polygonatum in recent years. However, up to now, there has been a lack of comprehensive studies on the active ingredients and their pharmacotoxicological effects related to cardiovascular diseases. Therefore, the main active components of Polygonatum (including Polysaccharides, Flavonoids, Saponins) and their biological activities were firstly reviewed in this paper. Furthermore, we summarized the pharmacological effects of Polygonatum's active components in preventing and treating CVDs, and its relevant toxicological investigations. Finally, we emphasize the potential of Polygonatum in the prevention and treatment of CVDs.

Simultaneous binding of quercetin and catechin to FOXO3 enhances IKKα transcription inhibition and suppression of oxidative stress-induced acute alcoholic liver injury in rats.

INTRODUCTION: Oxidative stress is one of the major contributors to acute alcoholic liver injury (AALI), which is a common alcoholic liver disease. Quercetin and catechin are flavonoid antioxidants present in plant foods and possess chemopreventive and chemotherapeutic activities. Quercetin and catechin are often included in the same meal and ingested together. While they show cooperative actions against oxidative damage, the underlying mechanisms behind their counteracting effects against oxidative stress-induced AALI remain poorly understood. OBJECTIVES: The aim of this study was to understand the mechanism underlying the enhanced antioxidant effect of quercetin-catechin combination to alleviate AALI in rats. METHODS: The ethanol (EtOH)-treated rats and H2O2-treated liver cells were used to demonstrate the enhanced antioxidant effect of quercetin and catechin. Then we used RNA-sequencing to compare quercetin alone, catechin alone and quercetin-catechin combination and then identified the critical role of IKKα combining with gene silencing and overexpression techniques. Its transcription factor, FOXO3 was found through yeast one-hybrid assay, luciferase reporter assay, EMSA and ChIP assay. Finally, the interaction between quercetin, catechin and FOXO3 was verified through molecular docking, UV-Vis absorption spectroscopy, fluorescence spectroscopy, and CD spectroscopy. RESULTS: The study demonstrated the enhanced antioxidant effect of a quercetin-catechin combination in EtOH-treated rats and in H2O2-treated liver cells. Quercetin and catechin cooperatively inhibited IKKα/p53 pathway and activated Nrf2 signaling pathway. IKKα was a critical negative regulator in their joint action. FOXO3 bound to IKKα promoter to regulate IKKα transcription. Quercetin and catechin influenced FOXO3-IKKα binding through attaching directly to FOXO3 at different sites and altering FOXO3's secondary structures. CONCLUSION: Our study revealed the mechanism of quercetin and catechin against oxidative stress-induced AALI through jointly interacting with transcription factor. This research opens new vistas for examining the joint effect of therapeutics towards functional proteins and confirms the chemopreventive effects of multiple flavonoids via co-regulation.

Harnessing astaxanthin-loaded diselenium cross-linked apotransferrin nanoparticles for the treatment of secretory otitis media.

Secretory otitis media (SOM) is a clinical condition characterized by the accumulation of fluids and oxidative stress in the middle ear, leading to hearing impairment and infection complications. One potential solution for mitigating oxidative stress associated with SOM is the use of antioxidants such as astaxanthin. However, its effectiveness is limited due to its poor bioavailability and rapid oxidation. Herein, we developed a novel diselenium-crosslinked apotransferrin enriched with astaxanthin (AST@dSe-AFT) nanoparticles to augment the transport of astaxanthin across biological membranes, resulting in increased bioavailability and reduced oxidative stress in SOM. Our research demonstrated that AST@dSe-AFT efficiently accumulated in the middle ear, allowing for controlled delivery of astaxanthin in response to reactive oxygen species and reducing oxidative stress. Additionally, AST@dSe-AFT stimulated macrophages to polarize towards M2 phenotype and neutrophils to polarize towards N2 phenotype, thereby facilitating an anti-inflammatory response and tissue restoration. Importantly, AST@dSe-AFT exhibited no toxicity or adverse effects, suggesting its potential for safety and future clinical translation. Our findings suggested that AST@dSe-AFT represents a promising approach for the treatment of secretory otitis media and other oxidative stress-related disorders.

Therapeutic Potential of Biochanin A in Herpes Simplex Keratitis.

Herpes simplex keratitis (HSK) is a blinding eye disease that is initiated by the herpes simplex virus type 1 (HSV-1). Resistance to acyclovir (ACV) and the side effects of corticosteroid drugs have become concerning issues, so it is crucial to develop new antivirals for treating HSK. In this study, we report that biochanin A (BCA), a naturally occurring flavonoid compound, provides multifaceted protective effects with anti-viral, anti-inflammatory, anti-oxidative stress and anti-apoptotic activities to alleviate HSK. The results show that BCA significantly inhibited HSV-1 replication in vitro and further proved that BCA principally influenced the early stage of virus infection. We reveal that BCA downregulated the expression of pro-inflammatory factors triggered by HSV-1, including TNF-α, RANTES, IL-1ß and IL-6. Furthermore, BCA treatment alleviated oxidative stress and apoptotic arising from HSV-1 infection. Lastly, we induced HSK in male C57BL/6 mice and treated them with either BCA or phosphate buffer solution (PBS) eye drops. We observed the ocular surface lesions; determined the virus load in the tear fluid, corneas as well as trigeminal ganglions (TGs); and detected the levels of inflammation and apoptosis in the corneas simultaneously. These results show that BCA inhibits HSV-1 and alleviates the corneal lesion degree. Our study illustrates that BCA is a promising therapeutic approach for application in treating HSK.

Shenqi formula delayed Alzheimer's disease-like symptoms by skn-1 pathway in Caernorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi formula is composed of Codonopsis pilosula (Cp) and Lycium barbarum (Lb), and it is traditionally used for promoting qi and nourishing the spleen, liver and kidney. Cp and Lb have been reported to improve cognitive performance in APP/PS1 mice, prevent the accumulation of Aß, and reduce the neurotoxicity of Aß to achieve the anti-Alzheimer's disease (AD) effect. AIM OF THE STUDY: Shenqi formula was explored the therapeutic effect on Caenorhabditis elegans AD pathological model and the underlying mechanism of action. MATERIALS AND METHODS: Paralysis assay and serotonin sensitivity assay was used to detect whether Shenqi formula can alleviate AD paralysis phenotype, and then DPPH, ABTS, NBT and Fenton methods were applied to investigate the scavenging capacity to free radical, ROS, ·O2- and ·OH of Shenqi formula in vitro. H2DCF-DA and MitoSOX™ Red were employed to measure ROS and .O2- accumulation, respectively. RNAi was used to knock down the expression of skn-1 and daf-16 related to oxidative stress resistance signalling pathway. Fluorescence microscopy was used to record the expression of SOD-3::GFP, GST-4::GFP, SOD-1::YFP, and the nuclear translocation of SKN-1 and DAF-16. Western blot assay was carried out to test Aß monomers and oligomers. RESULTS: Shenqi formula delayed the AD-like pathological characteristics in C. elegans, and the complete Shenqi formula was more effective than Cp or Lb alone. The effect of Shenqi formula on delaying worm paralysis was partially eliminated by skn-1 RNAi, but not daf-16 RNAi. Shenqi formula significantly inhibited the abnormal deposition of Aß protein, decreased Aß protein monomers and oligomers. It increased the expressions of gst-4, sod-1, and sod-3 similar to paraquat, companied by rise then fall of ROS and .O2- in AD worms. CONCLUSIONS: Shenqi formula at least partially depended on SKN-1 signalling pathway to exert its anti-AD effect, and it is potential to be used as a kind of health food to prevent the progress of AD.

Low-Molecular-Weight Chondroitin Sulfates Alleviate Simulated Microgravity-Induced Oxidative Stress and Bone Loss in Mice.

(1) Background: Many studies have shown that microgravity experienced by astronauts or long-term bedridden patients results in increased oxidative stress and bone loss. Low-molecular-weight chondroitin sulfates (LMWCSs) prepared from intact chondroitin sulfate (CS) have been demonstrated to possess good antioxidant and osteogenic activities in vitro. This study aimed to assess the antioxidant activity of the LMWCSs in vivo and evaluate their potential in preventing microgravity-induced bone loss. (2) Methods: we used hind limb suspension (HLS) mice to simulate microgravity in vivo. We investigated the effects of LMWCSs against oxidative stress damage and bone loss in HLS mice and compared the findings with those of CS and a non-treatment group. (3) Results: LMWCSs reduced the HLS-induced oxidative stress level, prevented HLS-induced alterations in bone microstructure and mechanical strength, and reversed changes in bone metabolism indicators in HLS mice. Additionally, LMWCSs downregulated the mRNA expression levels of antioxidant enzyme- and osteogenic-related genes in HLS mice. The results showed that overall effect of LMWCSs was better than that of CS. (4) Conclusions: LMWCSs protect against the bone loss caused by simulated microgravity, which may be related to their ability to reduce oxidative stress. LMWCSs can be envisaged as potential antioxidants and bone loss protective agents in microgravity.

Design and synthesis of salidroside analogs and their bioactivity against septic myocardial injury.

Cardiac tissue suffers much from sepsis, and the incidence of myocardial injury is high in septic patients. The treatment of sepsis myocardial injury (SMI) has been the focus of clinical medicine. Salidroside shows myocardial cell protection, anti-oxidation and anti- inflammation effects, and it is thought as one of the potential compounds to treat sepsis myocardial injury. However, its anti-inflammatory activity is lower and its pharmacokinetic properties are not ideal, which is far from clinical application. Here, a series of salidroside analogs were synthesized, and their bioactivities were evaluated from several aspects, including their anti-oxidant and anti-inflammatory activities in vitro and anti-sepsis myocardial injury activities in vivo. Of all the compounds which synthesized, compounds 2 and 3 exhibited stronger anti-inflammatory activities than the others; after treating LPS-stimulated RAW264.7 or H9c2 cells with each of them, the levels of IL-1ß, IL-6 and TNF-α were down-regulated in a dose-dependent manner. In the anti-oxidative stress injury test, compounds 2 and 3 not only markedly increased the survival rate of cells, and but also improved the cellular oxidative stress-related indicators MDA, SOD and cell damage marker LDH in a dose-dependent manner. In the LPS-induced septic rat myocardial injury models (in vivo), the two compounds also showed good bioactivities. They also reduced the expression of IL-1ß, IL-6 and TNF-α, and blocked cell damage by suppressing overhauled oxidation in septic rats. In addition, the myocardial injury was significantly improved and the inflammatory infiltration was reduced after treatment with the two compounds. In conclusion, the salidroside analogs (2 and 3) showed promising therapeutical effect on septic myocardial injury in LPS-model rats, and they could be good candidates for clinical trials against inflammation and septic myocardial injury.

Review on the protective mechanism of astragaloside IV against cardiovascular diseases.

Cardiovascular disease is a global health problem. Astragaloside IV (AS-IV) is a saponin compound extracted from the roots of the Chinese herb Astragalus. Over the past few decades, AS-IV has been shown to possess various pharmacological properties. It can protect the myocardium through antioxidative stress, anti-inflammatory effects, regulation of calcium homeostasis, improvement of myocardial energy metabolism, anti-apoptosis, anti-cardiomyocyte hypertrophy, anti-myocardial fibrosis, regulation of myocardial autophagy, and improvement of myocardial microcirculation. AS-IV exerts protective effects on blood vessels. For example, it can protect vascular endothelial cells through antioxidative stress and anti-inflammatory pathways, relax blood vessels, stabilize atherosclerotic plaques, and inhibit the proliferation and migration of vascular smooth muscle cells. Thus, the bioavailability of AS-IV is low. Toxicology indicates that AS-IV is safe, but should be used cautiously in pregnant women. In this paper, we review the mechanisms of AS-IV prevention and treatment of cardiovascular diseases in recent years to provide a reference for future research and drug development.

Integration of molecular docking, molecular dynamics and network pharmacology to explore the multi-target pharmacology of fenugreek against diabetes.

Fenugreek is an ancient herb that has been used for centuries to treat diabetes. However, how the fenugreek-derived chemical compounds work in treating diabetes remains unclarified. Herein, we integrate molecular docking and network pharmacology to elucidate the active constituents and potential mechanisms of fenugreek against diabetes. First, 19 active compounds from fenugreek and 71 key diabetes-related targets were identified through network pharmacology analysis. Then, molecular docking and simulations results suggest diosgenin, luteolin and quercetin against diabetes via regulation of the genes ESR1, CAV1, VEGFA, TP53, CAT, AKT1, IL6 and IL1. These compounds and genes may be key factors of fenugreek in treating diabetes. Cells results demonstrate that fenugreek has good biological safety and can effectively improve the glucose consumption of IR-HepG2 cells. Pathway enrichment analysis revealed that the anti-diabetic effect of fenugreek was regulated by the AGE-RAGE and NF-κB signalling pathways. It is mainly associated with anti-oxidative stress, anti-inflammatory response and ß-cell protection. Our study identified the active constituents and potential signalling pathways involved in the anti-diabetic effect of fenugreek. These findings provide a theoretical basis for understanding the mechanism of the anti-diabetic effect of fenugreek. Finally, this study may help for developing anti-diabetic dietary supplements or drugs based on fenugreek.

Zinc defends against Parthanatos and promotes functional recovery after spinal cord injury through SIRT3-mediated anti-oxidative stress and mitophagy.

INTRODUCTION: Spinal cord injury (SCI) is a central nervous system injury that is primarily traumatic and manifests as motor, sensory, and autonomic dysfunction below the level of damage. Our previous studies confirmed the ability of zinc to protect mitochondria, protect neurons and promote spinal cord recovery. However, the role of zinc in Parthanatos is unknown. AIM: We investigated the effects of zinc in Parthanatos from oxidative stress and mitophagy. We elucidated the role of SIRT3 in providing new ideas for treating spinal cord injury. THE RESULTS: Zinc protected SCI mice by regulating Parthanatos. On the one hand, zinc eliminated ROS directly through SIRT3 deacetylation targeting SOD2 to alleviate Parthanatos. On the other hand, zinc eliminated ROS indirectly through SIRT3-mediated promotion of mitophagy to alleviate Parthanatos. CONCLUSION: Zinc defends against Parthanatos and promotes functional recovery after spinal cord injury through SIRT3-mediated anti-oxidative stress and mitophagy.

Quality Characteristics of Citrus Peel Jelly.

Citrus peels are high in flavonoids and can help with nausea, indigestion, and phlegm. Furthermore, the peel is higher in dietary fiber and phenolic compounds than the fruit. However, every year, around 40,000∼120,000 tons of citrus peels are discarded as waste. As a result, citrus peel jelly was created, which can be reused as a functional food. In this study, salinity, color, texture, and antioxidant properties were measured by adding citrus peel powder at 0%, 1%, 3%, 5%, and 7%, respectively. The salinity decreased as the amount of addition increased (P<0.001). The L-value of chromaticity decreased significantly (P<0.001). The a-, b-value increased significantly (P<0.001). As the addition amount increased, the hardness decreased significantly (P=0.002). Total polyphenols, flavonoids, 2,2-diphenyl-1-picrylhydrazyl scavenging capacity, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging capacity all increased statistically significantly (P<0.001). Through this study, we confirmed the quality characteristics of citrus peel jelly. Citrus peel jelly, which is high in antioxidant activity, is expected to increase the use of peel and functional foods.

Bioactive Compounds as Inhibitors of Inflammation, Oxidative Stress and Metabolic Dysfunctions via Regulation of Cellular Redox Balance and Histone Acetylation State.

Bioactive compounds (BCs) are known to exhibit antioxidant, anti-inflammatory, and anti-cancer properties by regulating the cellular redox balance and histone acetylation state. BCs can control chronic oxidative states caused by dietary stress, i.e., alcohol, high-fat, or high-glycemic diet, and adjust the redox balance to recover physiological conditions. Unique functions of BCs to scavenge reactive oxygen species (ROS) can resolve the redox imbalance due to the excessive generation of ROS. The ability of BCs to regulate the histone acetylation state contributes to the activation of transcription factors involved in immunity and metabolism against dietary stress. The protective properties of BCs are mainly ascribed to the roles of sirtuin 1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (NRF2). As a histone deacetylase (HDAC), SIRT1 modulates the cellular redox balance and histone acetylation state by mediating ROS generation, regulating nicotinamide adenine dinucleotide (NAD+)/NADH ratio, and activating NRF2 in metabolic progression. In this study, the unique functions of BCs against diet-induced inflammation, oxidative stress, and metabolic dysfunction have been considered by focusing on the cellular redox balance and histone acetylation state. This work may provide evidence for the development of effective therapeutic agents from BCs.

The Protective Effect of the Asystasia chelonoides Extracts on Hypertensive Nephropathy Rats.

BACKGROUND: Hypertensive nephropathy (HN) is one kind of kidney disorders caused by long-term uncontrolled hypertension, usually resulting in severe kidney damage, including inflammation and oxidative stress, no matter in cells or tissues, from patients with nephropathy. In recent years, nephropathy accompanied by hypertension is becoming one of the main causes for kidney replacement therapy, but few effective treatments have been reported for HN treatment. Asystasia chelonoides (AC) is a kind of plant with the effects of anti-inflammation, lowering blood pressure, and anti-oxidative stress. Still, the therapeutic effect of AC in HN rats is not clear. METHODS: To establish HN model by feeding high sugar and high fat diet spontaneously hypertensive rats. Blood measurement, HE staining, PAS staining and biochemical analysis and were used to assess the therapeutic effects of AC extracts and western blotting analyzed the underlying mechanisms of AC extracts treatment in the HN rat model. RESULTS: AC extracts could significantly lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) in HN rats; and reduce the expression of total protein (TP), blood urea nitrogen (BUN), microalbuminuria (MALB), creatinine (Cr), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) concentrations, and also could down-regulate expression of IL-6, MDA and AGEs, up-regulate the expression of SOD in HN rats; HE staining and PAS staining demonstrated that AC extracts could alleviate the histopathological changes in HN rats; western blotting demonstrated that AC extracts could up-regulate the expression of PPARγ and down-regulate the expression of TGFß1 and NF-кB in HN rats. CONCLUSION: The finding of the article demonstrated that AC extracts had the better therapeutic effect for HN, and provided the pharmacological evidences for AC extracts treatment for HN.

Tumor-specific activated nano-domino-CRISPR to amplify intrinsic oxidative and activate endogenous apoptosis for spatiotemporally specific therapy.

As a non-invasive modality with unique spatiotemporal selectivity, photodynamic therapy (PDT) is emerging as a candidate in cancer treatment. Nevertheless, intrinsic anti-oxidative stress factors represented by the up-regulated B cell lymphoma/leukemia-2 (Bcl-2) and the attenuated-PDT activity along the light path are still the major concerns, therefore exploring the PDT-based synergistic and augmented strategies is challenging but imperative. Here, a tumor-specific activated nano-domino-CRISPR (TAN) is fabricated and coloaded with chlorins e6 (Ce6) and CRISPR/Cas9 plasmid targeting Bcl-2 gene to amplify intrinsic oxidative and activate endogenous apoptosis for spatiotemporally specific therapy. Inert TAN acting as the first domino is activated in enzyme-abundant intracellular environment to strip the shell. The activated TAN pushes the subsequent dominos, encompassing orderly efficient lysosomal escape, gene delivery, precise disruption of Bcl-2 protein and PDT effect induced by the shell containing Ce6 with light to trigger further domino effects. For tumor cells located superficial sites, down-regulated Bcl-2 reduces cellular GSH content and potentiates oxidative stress of PDT. Cells located deep sites are triggered endogenous apoptosis by disruption of Bcl-2. The high anti-tumor efficacy of TAN is demonstrated both in vitro and in vivo. Overall, our work offers a valuable emerging approach for conquering the therapeutical deficiency of PDT.

Bioactive Compounds in Moringa oleifera: Mechanisms of Action, Focus on Their Anti-Inflammatory Properties.

Moringa oleifera (M. oleifera) is a tropical tree native to Pakistan, India, Bangladesh, and Afghanistan; it is cultivated for its nutritious leaves, pods, and seeds. This scientific study was conducted to outline the anti-inflammatory properties and mechanisms of action of bioactive compounds from M. oleifera. The existing research has found that the plant is used in traditional medicine due to its bioactive compounds, including phytochemicals: flavonoids and polyphenols. The compounds are thought to exert their anti-inflammatory effects due to: (1) inhibition of pro-inflammatory enzymes: quercetin and kaempferol inhibit the pro-inflammatory enzymes (cyclooxygenase and lipoxygenase); (2) regulation of cytokine production: isothiocyanates modulate signaling pathways involved in inflammation, such as the nuclear factor-kappa B (NF-kappa B) pathway; isothiocyanates inhibit the production of pro-inflammatory cytokines such as TNF-α (tumor necrosis factor α) and IL-1ß (interleukin-1ß); and (3) antioxidant activity: M. oleifera contains flavonoids, polyphenols, known to reduce oxidative stress and inflammation. The review includes M. oleifera's effects on cardiovascular protection, anti-hypertensive activities, type 2 diabetes, inflammatory bowel disease, and non-alcoholic fatty liver disease (NAFLD). This research could prove valuable for exploring the pharmacological potential of M. oleifera and contributing to the prospects of developing effective medicines for the benefit of human health.