Acute myocardial ischemia (AMI) is a life-threatening cardiovascular disorder characterized by excessive oxidative stress and persistent inflammatory cascades, yet safe multi-target natural therapeutic agents remain scarce. Cinnamomum migao is a well-known Miao ethnic medicine used for cardiovascular conditions, yet its cardioprotective effects and mechanisms remain largely unclear. This study investigated the efficacy and underlying mechanism of C. migao ethyl acetate extract (MGE) against AMI. MGE significantly improved the viability of H9c2 cardiomyocytes subjected to OGD/R injured. UPLC-MS/MS and molecular networking identified 30 constituents in MGE, among which sesquiterpenoids predominated. In ISO-induced AMI rats, MGE dose-dependently mitigated myocardial injury, as reflected by reduced ST-segment elevation, serum CK-MB and LDH levels, and alleviated histopathological damage. MGE enhanced SOD and CAT activities, decreased MDA content, and inhibited the secretion of TNF-α, IL-6 and IL-1β. Mechanistically, MGE downregulated the expression of NOX4, HIF-1α, p38 MAPK and NF-κB p65, while activating the Nrf2/HO-1 pathway. Oxyphyllenone A and magnodelavin C were identified as key active sesquiterpenoids that stably bound to IL-17 and TNF. Collectively, MGE alleviates AMI injury via anti-oxidative, anti-hypoxic, and anti-inflammatory effects through modulation of the HIF-1α/Nrf2/NF-κB/MAPK axis downstream of oxidative stress, with sesquiterpenoids serving as its key bioactive components. This work provides robust experimental evidence supporting C. migao as a promising natural antioxidant candidate for the prevention and treatment of AMI.

Indocalamus latifolius (IL), a traditional Chinese food packaging material, possesses bioactive compounds with antioxidant and anti-inflammatory properties. This study investigated IL’s aqueous extract (ILAE) protective effects against acute alcohol intoxication (AAI) and chronic alcoholic gastric injury (AGI). In the AAI model, ILAE enhanced ADH and ALDH activities, reduced intoxication rate, shortened sobering time. In the chronic AGI model, ILAE alleviated gastric injury, increased SOD and PGE2, and decreased MDA, TNF-α, IL-6, IL-8, TGF-β1, and MPO levels. Network pharmacology predicts that the PI3K-Akt pathways is the main protective mechanisms. Molecular docking confirmed strong binding affinities between stigmasterol and key target proteins. Furthermore, ILAE downregulated PI3K, AKT, and NF-κB protein expression in ethanol-induced GES-1 cells. These findings suggest that ILAE protects against AAI and AGI by activating the PI3K/AKT pathway regulate oxidative stress and inflammation. Collectively, ILAE shows promise as a functional food component for preventing alcohol-related disorders.

Aristolochic acid I (AAI), which is one of the main forms of aristolochic acid, can cause aristolochic acid nephropathy. Abnormal activation or inhibition of the Wnt7b/(3-catenin signaling pathway may lead to the occurrence and development of kidney disease. This study aimed to investigate the effect of the Wnt7b/(3-catenin signaling pathway on the damage and repair processes of renal tubular epithelial cells (RTECs) using mouse and zebrafish models of acute aristolochic acid intoxication. Our data revealed that after mice were exposed to 5 mg/ kg/day AAI for 4 days and 6 days the expression of Wnt7b on the villi of RTECs increased, the expression of (3-catenin on the cytoplasm decreased, and the expression of (3-catenin in the nucleus increased. The protein expression levels of PCNA and Kim-1 increased. After zebrafish at 3 days post fertilization were exposed to 2, 4, and 8 mu g/mL AAI for 24 h, the results indicated that treatment with AAI resulted in a decrease in the number of RTECs and the occurrence of apoptosis. Importantly, after knockout of the Wnt7ba gene, damage to RTECs in zebrafish larvae was aggravated, the mRNA expression level of PCNA decreased, and that of Kim-1 increased. In addition, we found that AAI exhibits developmental toxicity in fertilized zebrafish eggs. As a result, AAI leads to abnormal activation of the Wnt7b/(3-catenin signaling pathway, which affects the repair of renal tubular injury by activating the downstream protein PCNA. The Wnt7ba gene may serve as a potential therapeutic target to promote repair after renal tubular injury.

Background:Dangguiliuhuang Tang (DGLHT), a classic traditional Chinese medicine formula, has long been used to treat type 2 diabetes mellitus (T2DM). Nevertheless, its therapeutic efficacy, pharmacological foundation, and underlying mechanisms warrant further scientific exploration. Methods:Ultra-high-performance liquid chromatography coupled with Thermo Vanquish UHPLC-Thermo Q Exactive HFX (UHPLC-QE-MS) was utilized to identify the chemical components of DGLHT. A potential therapeutic network for DGLHT in treating T2DM was constructed using network pharmacology. Untargeted metabolomics techniques were applied to reveal the differential effects of DGLHT on T2DM, and 16S rDNA amplification sequencing technology was used to investigate the differential metabolic regulation of gut microbiota in T2DM mice treated with DGLHT. Molecular biomedical experimental methods were combined to validate and analyze expression levels of the relevant proteins in the liver. A correlation analysis between the active ingredients of DGLHT and the differential gut microbiota was established. Results:DGLHT improved glycemia, glucose tolerance, and liver injury in T2DM mice. A total of 38 major components were identified. Core targets included mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 3 (MAPK3), non-receptor tyrosine kinase (TNK), C-X-C motif chemokine ligand 8 (CXCL8), and serine/threonine kinase 1 (AKT1). DGLHT significantly altered the serum metabolic profile and gut microbiota composition in T2DM mice. These alterations affected inflammation-related Toll-like receptor signaling pathways, phosphorylation-associated ErbB signaling pathways, and functional substance metabolism related to bile secretion, cholesterol metabolism, biosynthesis of unsaturated fatty acids, protein digestion and absorption, cysteine and methionine metabolism, carbohydrate metabolism, intestinal membrane transport, and amino acid metabolism. DGLHT modulated protein expression in several key signaling pathways, including the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) pathway, phosphatidylinositide 3-kinase (PI3K)/protein kinase B (AKT)/glucose transporter type 4 (GLUT4) pathway, AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferators-activated receptor γ coactivator 1 alpha (PGC-1α) pathway, and heme oxygenase 1 (HO-1)/superoxide dismutase (SOD2)/catalase (CAT) pathway. The Candida genus and gamma-linolenic acid exhibited the strongest correlation. Conclusion:DGLHT alleviates T2DM insulin resistance via multi-pathway regulation of inflammation, energy metabolism, and oxidative stress, mediated through metabolic and gut microbiota modulation.

Introduction:This study investigates the pathological progressions in kidneys affected by aristolochic acid nephropathy (AAN) and explores the molecular mechanisms underlying the fibrotic process, specifically focusing on the Wnt7b/β-catenin signaling pathway. Methods:Both mice and human kidney-2 (HK-2) cells were treated with aristolochic acid I (AAI). In mice, we monitored blood urea nitrogen (BUN), serum creatinine (Scr), kidney injury molecule-1 (KIM-1), pathological modifications of renal tubular epithelial cells (RTECs), and fibrosis degrees during acute/chronic disease phases. Wnt7b/β-catenin expression was evaluated through transcriptome analysis and laboratory assays (immunohistochemistry, Western blotting, immunoelectron microscopy) in acute AAN and cultured cells. Concurrent assays measured representative proteins: Aquaporin 1 (AQP1), Topoisomerase IIα (TOP2A), Vascular Cell Adhesion Molecule-1 (VCAM-1), and α-smooth muscle actin (α-SMA) in chronic AAN RTECs. Results:AAI increased Scr, BUN, and KIM-1 levels by causing RTEC necrotic shedding in acute stages and promoted renal interstitial fibrosis chronically. Elevated Wnt7b pathway proteins enhanced damaged RTEC regeneration, with regenerated cells expressing mesenchymal proteins VCAM-1 and α-SMA. Discussion:The Wnt7b/β-catenin signaling pathway connects acute tubule damage to fibrosis, explaining AAN's pathological continuum. These findings clarify how acute injury progresses to chronic fibrosis in AAN.

Gastric ulcers (GUs) are superficial diffuse lesions of the gastric mucosa that are characterised by being vulnerable to infection, difficult to cure and liable to recur. Bletilla ochracea Schltr. (BO) has the effects of astringent hemostasis, muscle growth and pain relief. We examined the effects of BO on acute GUs and their potential mechanisms from the perspectives of inflammation, oxidative stress and gut microbiota. Results indicated that BO alleviated pathological injury to the gastric mucosa and markedly alleviated oxidative stress and inflammation. In addition, BO significantly upregulated the levels of Nrf2, HO-1, NQO1 protein, and downregulated the levels of NF-κB p65, TLR4 protein. Moreover, BO significantly increased promoting the nuclear transfer of Nrf2 and markedly reduced the nuclear translocation of NF-κB p65. Furthermore, BO effectively modulated gut microbiota by increasing the diversity of species and relative abundance. Our study provided evidence that BO alleviated ethanol-induced acute GUs by activating the Nrf2/HO-1 and inhibiting the NF-κB p65/TLR4 signalling pathway, regulating dysbiosis of gut microbiota.

Doxorubicin (DOX) is widely employed in anticancer therapy, but its clinical application is constrained by its cardiotoxic effects. Trillin, a bioactive compound derived from Trillium tschonoskii Maxim., has been identified as a natural antioxidant possessing cardioprotective properties. This study aimed to ascertain whether trillin can protect against DOX-induced cardiotoxicity (DIC) through its inherent antioxidant capabilities. In vivo studies, C57BL/6 mice were administered DOX (5 mg/kg i.p.) via intraperitoneal injection once weekly for a total of five consecutive weeks and received trillin (25, 50 and 100 mg/kg i.g.) through intragastric administration once daily for six weeks. In vitro studies, H9c2 cardiomyocytes were utilized to verify the protective efficacy of trillin (0.5, 1 and 2 μM) against DIC. Trillin significantly mitigated DOX-induced myocardial damage, which encompassed improvements in left ventricular function, reductions in serum cardiac enzymes levels, and diminution of heart cell vacuolation. Moreover, trillin effectively attenuated DIC while preserving the anticancer efficacy of DOX. Trillin also alleviated oxidative injury by elevating levels of SOD and GSH and reducing MDA levels. Additionally, trillin restored the expression of Nrf2 and HO-1 in mouse hearts and H9c2 cardiomyocytes treated with DOX. Trillin safeguarded against DIC by inhibiting oxidative stress via upregulation of the Nrf2/HO-1 pathway. These findings furnish evidence suggesting trillin may serve as a therapeutic agent for the prevention of DIC.

Aristolochic acid I (AAI), which is one of the main forms of aristolochic acid, can cause aristolochic acid nephropathy. Abnormal activation or inhibition of the Wnt7b/β-catenin signaling pathway may lead to the occurrence and development of kidney disease. This study aimed to investigate the effect of the Wnt7b/β-catenin signaling pathway on the damage and repair processes of renal tubular epithelial cells (RTECs) using mouse and zebrafish models of acute aristolochic acid intoxication. Our data revealed that after mice were exposed to 5 mg/kg/day AAI for 4 days and 6 days the expression of Wnt7b on the villi of RTECs increased, the expression of β-catenin on the cytoplasm decreased, and the expression of β-catenin in the nucleus increased. The protein expression levels of PCNA and Kim-1 increased. After zebrafish at 3 days post fertilization were exposed to 2, 4, and 8 μg/mL AAI for 24 h, the results indicated that treatment with AAI resulted in a decrease in the number of RTECs and the occurrence of apoptosis. Importantly, after knockout of the Wnt7ba gene, damage to RTECs in zebrafish larvae was aggravated, the mRNA expression level of PCNA decreased, and that of Kim-1 increased. In addition, we found that AAI exhibits developmental toxicity in fertilized zebrafish eggs. As a result, AAI leads to abnormal activation of the Wnt7b/β-catenin signaling pathway, which affects the repair of renal tubular injury by activating the downstream protein PCNA. The Wnt7ba gene may serve as a potential therapeutic target to promote repair after renal tubular injury.

In China, Phrynium capitatum Willd. (PC) leaves have long been utilized for wrapping glutinous rice to prepare Zongzi, a cultural delicacy. Additionally, the water extract of PC leaves has been used as a folk remedy to alleviate symptoms of alcoholism for over a millennium. However, a systematic investigation into its therapeutic properties has been lacking. To address this gap, an acute alcoholism (AA) mouse model and a chronic alcoholic liver injury (ALI) rat model were established to investigate the protective effects and underlying mechanisms of the PC leaves water extract. The results revealed that the PC leaves water extract significantly decreased the rate of intoxication in AA mice, reduced ethanol concentration, and enhanced the activity of alcohol dehydrogenase. In the chronic ALI rat model, the PC leaves water extract effectively lowered serum transaminase levels and alleviated pathological liver damage. Furthermore, PC leaves water extract enhanced antioxidant capacity, decreased markers of inflammation in the liver, with the mechanism associated with regulation of the NF-κB and Nrf2/HO-1 pathways. Network pharmacological analysis and molecular docking validation have identified the key active ingredients in PC leaves water extract that protect against AA and chronic ALI. These ingredients include kaempferol, sedanolide, α-aspartylphenylalanine, isovaleric acid, ferulic acid, ligustilide, and isoscopolamine. Collectively, these findings suggest that PC leaves water extract holds significant potential for preventing and treating of both AA and ALI.

Diabetic nephropathy (DN), a common microvascular complicating disease of diabetes. Lupenone, a pentacyclic triterpenoid, has anti-inflammatory effects and can prevent type 2 diabetes mellitus and treat renal damage, however, the effects and mechanisms of lupenone in DN remain unclear. Thereby,the MTT method was used to investigate the antiproliferative effect of lupenoneon the cell line rat glomerular mesangial cells (HBZY-1). Molecular docking was used to investigate the combination of lupenone and MCP-1, IL-1β, TNF-α, IKKβ, IκBα, and NF-κB p65 proteins. The expression of mRNA of the pro-inflammatory cytokines (MCP-1, IL-1β and TNF-α) and the NF-κB signalling pathway in HBZY-1 cells were assessed by RT-PCR. The protein expressions of pro-inflammatory cytokines and NF-κB pathway were got by Western blot. Result showed that lupenone inhibited the proliferative activity of HBZY-1 cells at non-cytotoxic concentrations. Molecular docking results showed that lupenone combined well with the target proteins. Moreover, lupenone could significantly reduced the mRNA and protein expressions for pro-inflammatory cytokines and IKKβ, p-p65 and p-IκBα. Lupenone may play an anti-inflammatory role in DN treatment by inhibiting the NF-κB signalling pathway. These results provided a new understanding of the pharmacological mechanisms of lupenone in treatment of DN.

Ethnopharmacological relevanceIron is an essential micronutrient for maintaining physiological activities, especially for highly active cardiomyocytes. Inappropriate iron overload or deficiency has a significant impact on the incidence and severity of cardiovascular diseases (CVD). Iron overload exerts potentially deleterious effects on doxorubicin (DOX) cardiomyopathy, atherosclerosis, and myocardial ischemia-reperfusion injury (MI/RI) by participating in lipid peroxides production. Notably, iron overload-associated cell death has been defined as a possible mechanism for ferroptosis. At present, some traditional herbal medicines and extracts have been included in the study of regulating iron overload and the subsequent therapeutic effect on CVD.Aim of the studyTo give an outline of iron metabolism and ferroptosis in cardiomyocytes and to focus on herbal medicines and extracts to prevent iron overload in CVD.Materials and methodsLiterature information was systematically collected from ScienceDirect, PubMed, Google Scholar, Web of Science, China National Knowledge Infrastructure, WanFang data, as well as classic books and clinical reports.ResultsAfter understanding the mechanism of iron overload on CVD, this paper reviews the therapeutic function of various herbal medicines in eliminating iron overload in CVD. These include Chinese herbal compound prescriptions (Salvia miltiorrhiza injection, Gegen Qinlian decoction, Tongxinluo, Banxia-Houpu decoction), plant extracts, phenylpropanoids, flavonoids, terpenoids, and polyphenols. Among them, flavonoids are considered to be the most promising compounds because of their prominent iron chelation. Mechanically, these herbal medicines act on the Nrf2 signaling pathway, AMPK signaling pathway, and KAT5/GPX4 signaling pathway, thereby attenuating iron overload and lipid peroxidation in CVD.ConclusionOur review provides up-to-date information on herbal medicines that exert cardiovascular protective effects by modulating iron overload and ferroptosis. These herbal medicines hold promise as a template for preventing iron overload in CVD.

Pathogenesis and therapeutic drugs for ulcerative colitis (UC) have plagued researchers worldwide. In this study, therapeutic targets, and drugs from Chinese medicines for UC were screened using bioinformatics. We downloaded five datasets from the GEO database and three machine learning algorithms were used for screening diagnostic biomarkers of UC. Combined with the differential genes for UC, gene sets related to bile acid metabolism, short-chain fatty acids, apoptosis, pyroptosis, G-protein-coupled receptors, mitochondria, and autophagy were collected to screen the core targets, and analyze the association of therapeutic genes (diagnostic biomarkers and core targets) with immune cells. In addition, screening ingredients of Chinese medicines based on UC therapeutic targets was performed. Molecular docking, molecular dynamics simulation, and literature validation were also performed. The screening yielded 37 key therapeutic targets, including 5 diagnostic biomarkers (CCL11, CXCL1, PDZK1IP1, TIMP1, and UGT2A3) and 32 core targets based on hot gene sets. Immune cell infiltration was strongly associated with therapeutic targets in UC, especially neutrophils, macrophages, mast cells, and dendritic cells. Furthermore, a total of 33 compounds with high safety had been recognized as having potential to mitigate UC by reverse prediction from Chinese medicines, and molecular docking, molecular dynamics simulation, and literature reports preliminarily validated the screening results. Although further experimental validation is needed, this work provides some potential therapeutic targets and drugs from Chinese medicines against UC.

To investigate the safety of Indocalamu Iatifolius McClur leaves sold in the market, a study was conducted using Indocalamu Iatifolius McClur leaves randomly collected from an online store and a large supermarket. Acute toxicity experiments were performed on mice, and their body weight was monitored for 14 days after administration. After the observation period, blood samples were collected for biochemical analysis, and organ pathology was examined. Then, the content of copper (Cu), lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), and the residues of nine organochlorine pesticides in Indocalamu Iatifolius McClur leaves were measured according to the National Food Safety Standard (GB/T5009-2003) and the pesticide residue determination methods in the 2020 edition of the Chinese Pharmacopoeia. The results showed that the mice in the Indocalamu Iatifolius McClur leaves (online store) group experienced mortality and severe liver and lung damage. The levels of lead, cadmium, mercury, arsenic, and the nine organochlorine pesticides met the relevant standards and regulations. However, the copper content in the Indocalamu Iatifolius McClur leaves (online store) group was nearly 80 times higher than that in the supermarket group. Mice in the Indocalamu Iatifolius McClur leaves (supermarket) group remained healthy without any abnormalities, and the levels of harmful metals and organochlorine pesticides complied with the standards and regulations. The study suggests the need for regulatory policies and safety standards for the sale of Indocalamu Iatifolius McClur leaves.

Hyperglycemia and renal fibrosis play critical roles in the occurrence and development of diabetic complications such as diabetic nephropathy (DN). Lupenone, a stable pentacyclic triterpenoid compound, has anti-hyperglycemic and anti-renal fibrosis activities. Previous research has confirmed that lupenone can improve renal fibrosis in type 2 diabetic nephropathy by regulating TGF-β/Smad/CTGF signaling pathway. However, the binding power of lupenone with its related targets has not been confirmed, and it is unclear whether it exerts anti-renal fibrosis effects as a prototype component. Therefore, the aim of this study was to identify the underlying mechanism of lupenone on anti-renal fibrosis based on the TGF-β/Smad/CTGF signaling pathway and elucidate their binding ability using molecular docking and in vitro cell experiments. Molecular docking results suggested that lupenone combined well with fibronectin, TGF-β1, TβRI, TβRII, Smad2, Smad3, Smad4, Smad7 and Smurf2, respectively. And lupenone could significantly reduce high glucose-induced MCs cytotoxicity. Furthermore, lupenone significantly downregulated the mRNA and protein expression of collagen-I, collagen-IV, fibronectin, TGF-β1, p-TβRI/TβRI, TβRII, p-Smad2/Smad2, p-Smad/Smad3, Smad4, Smurf2, and CTGF in high glucose-induced MCs, with the best effect observed in the high-dose lupenone group. These results concluded that lupenone could inhibit the generation of fibrosis factors collagen-I, collagen-IV, and fibronectin and delay the process of fibrosis by regulating the TGF-β/Smad/CTGF signaling pathway in MCs.

Liquid chromatography-mass spectrometry (LC-MS) was used to identify and analyze the main components of Da Hong Pao, Zunyi black tea, and Yunnan Pu'er tea extracts, explore the effects of brewing times on chemical composition, and analyze the differential components using chemometrics. Subsequently, network pharmacology and molecular docking techniques were employed to explore the potential active ingredients and mechanisms of action in combating hypertension (HTN). This study identified eight key chemical constituents of the three teas, with significant differences in their contents. Yunnan Pu'er tea exhibited superior endurance for multiple infusions compared to the other teas. The research results clearly distinguished the three teas, with key components contributing to quality disparities identified as PCA, GC, gallic acid, and caffeine. The tea exerts anti-HTN effects through multiple pathways. The results of eight chemical components and core targets related to HTN exhibited favorable binding affinities. Our study suggested that Da Hong Pao, Zunyi black tea, and Yunnan Pu'er tea exhibit certain quality differences, and the overall quality of Yunnan Pu'er tea surpasses that of the other teas, though specific differences require further investigation. Moreover, the eight identified components from the three teas are all active components in combating HTN, and network pharmacology comprehensively elucidates the mechanism of tea's anti-hypertensive effect. These findings provide more potential key targets for the treatment of HTN by drinking tea. PRACTICAL APPLICATION: Eight common components were identified in Da Hong Pao, Zunyi black tea, and Yunnan Pu'er water extract, with significant differences in content. Yunnan Pu'er has better overall quality compared to Da Hong Pao and Zunyi black tea. The study provides more potential key targets for the treatment of hypertension by drinking tea.

Lupenone has been reported to possess numerous medicinal values and gives a positive antidiabetic effect. But the mechanism of preventing and treating type 1 diabetes has not been elucidated in type 1 diabetic rats. This study investigated the effects and mechanism of action of lupenone in preventing and treating type 1 diabetes by network pharmacology and diabetic rats. The blood glucose, glycosylated hemoglobin (HbA1c), insulin, and inflammatory factors in the pancreas of rats with type 1 diabetes were measured, and histopathological changes were observed after treatment with lupenone. The pharmacological network of ‘component-target-disease’ was constructed on diabetic rats. Gene function enrichment, the Kyoto Encyclopedia of Genes and Genomes pathway analysis, and molecular docking were performed. The results showed that lupenone can decrease fasting blood glucose and HbA1c levels, increase insulin content and interleukin (IL)-4, IL-10, and decrease IL-6, transforming growth factor β and tumor necrosis factor α levels in the pancreas. Furthermore, ten targets were identified, and 50 signal pathways closely related to type 1 diabetes and inflammation were screened by network pharmacology, including insulin resistance, type II diabetes, type I diabetes, insulin signal pathway, mitogen activated protein kinase (MAPK) signal pathway, and tumor necrosis factor (TNF) signal pathway. The docking affinity of potential targets and lupenone were between -3.3 and -9.8, among which caspase-3 (CASP3), cyclin-dependent kinase 4 (CDK4), inhibitor of kappaB kinase beta (IKBKB), transforming growth factor beta-1 (TGFB1), and TNF had high binding abilities. Thus, lupenone has the potential to be developed as a new drug for treating type 1 diabetes.

Background: Type 2 diabetic nephropathy is a common diabetic complication and the main cause of death in patients with diabetes. Research has aimed to find an ideal drug with minimal side effects for treating this disease. Banana peel has been shown to be anti-diabetic, with lupenone isolated from banana peel exhibiting antidiabetic and anti-inflammatory activities; However, the effects of lupenone on type 2 diabetic nephropathy are largely unknown. Purpose: This study aimed to investigate the ameliorative effect of lupenone on type 2 diabetic nephropathy, and its mechanism from both anti-inflammatory and anti-fibrotic perspectives. Methods: Spontaneous type 2 diabetic nephropathy db/db mouse models were given three levels of lupenone (24 or 12 or 6 mg/kg/d) via intragastric administration for six weeks, and irbesartan treatment was used for the positive control group. We explored the effects and mechanism of lupenone action using enzyme-linked immunosorbent assay, automatic biochemical analyzer, hematoxylin-eosin and Masson staining, real time-PCR, and western blotting. Concurrently, a high-sugar and high-fat diet combined with a low-dose streptozotocin-induced type 2 diabetic nephropathy rat model was used for confirmatory research. Results: Lupenone administration maintained the fasting blood glucose; reduced glycosylated hemoglobin, insulin, and 24 h proteinuria levels; and markedly regulated changes in biochemical indicators associated with kidney injury in serum and urine (including 24 h proteinuria, micro-albumin, N-acetyl-beta-D-glucosaminidase, alpha 1-micro-globulin, creatinine, urea nitrogen, uric acid, total protein, and albumin) of type 2 diabetic nephropathy mice and rats. Hematoxylin-eosin and Masson staining as well as molecular biology tests revealed that inflammation and fibrosis are the two key processes affected by lupenone treatment. Lupenone protected type 2 diabetic nephropathy kidneys by regulating the NF-kappa B-mediated inflammatory response and TGF-beta 1/Smad/CTGF pathway-associated fibrosis. Conclusion: Lupenone has potential as an innovative drug for preventing and treating diabetic nephropathy. Additionally, it has great value for the utilization of banana peel resources.

Statins are the first choice for lowering low-density lipoprotein cholesterol (LDL-C) and preventing atherosclerotic cardiovascular disease (ASCVD). However, statins can also upregulate proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn might limits the cholesterol-lowering effect of statins through the degradation of LDL receptors (LDLR). Di’ao Xinxuekang (DXXK) capsule, as a well-known traditional Chinese herbal medicine for the prevention and treatment of coronary heart disease, can alleviate lipid disorders and ameliorate atherosclerosis in atherosclerosis model mice and downregulate the expression of PCSK9. In this study, we further explored whether DXXK has a synergistic effect with atorvastatin (ATO) and its underlying molecular mechanism. The results showed that both ATO monotherapy (1.3 mg/kg) and ATO combined with DXXK therapy significantly lowered serum lipid levels and reduced the formation of atherosclerotic plaques and the liver lipid accumulation. Moreover, compared with ATO monotherapy, the addition of DXXK (160 mg/kg) to the combination therapy further lowered LDL-C by 15.55% and further reduced the atherosclerotic plaque area by 25.98%. In addition, the expression of SREBP2, PCSK9 and IDOL showed a significant increase in the model group, and the expression of LDLR was significantly reduced; however, there were no significant differences between the ATO (1.3 mg/kg) and the model groups. When ATO was combined with DXXK, the expression of LDLR was significantly increased and was higher than that of the model group and the expression of SREBP2 and PCSK9 in the liver was also significantly inhibited. Moreover, it can be seen that the expression of SREBP2 and PCSK9 in the combination treatment group was significantly lower than that in the ATO monotherapy group (1.3 mg/kg). Besides, the expression of IDOL mRNA in each treatment group was not significantly different from that of the model group. Our study suggests that DXXK might have a synergistic effect on the LDL-C lowering and antiatherosclerosis effects of ATO through the SREBP2/PCSK9 pathway. This indicates that a combination of DXXK and ATO may be a new treatment for atherosclerosis.

Located in chloroplast. The vitro enzymatic property verification CqMSRA5.1 can specifically reduce type methionine sulfoxide and belongs to MSRA family. Arabidopsis wild type Col 0, CqMSRA5.1 transformed Arabidopsis overexpression line and msra5 Arabidopsis mutant were used as materials to carryout phenotypic experiments of simulated osmotic stress treatment and soil drought treatment. The above results showed CqMSRA5.1. Enhance the resistance of Arabidopsis to osmotic stress by regulatcan enhance the resistance of Arabidopsis to osmotic stress by regulating the balance of the balance of ROS. The interaction protein of MSRA5 was predicted and analyzed by bioinformatics technology. Glutathione synthase 2 (GSH2) was predicted as the potential interaction protein of MSRA5. Yeast two hybrid experiment and two molecule fluorescence complementary experiment confirmed that quinoa glutathione synthase 2 gene (GSH2) and CqMSRA5.1 was interacted with each other. Through protein simulation binding analysis, it is found that the specific region of interaction is met residue 193 of CqGSH2. The pharmacological phenotype experiment with GSH specific inhibitor BSO showed that BSO could significantly inhibit CqMSRA5.1. The above CqMSRA5.1and CqGSH2 interact structurally.

Doxorubicin (DOX) is an effective antitumor drug; however, but its clinical application is seriously limited by the cardiotoxicity induced by its use. Recent studies have found that ferroptosis is an important mechanism underlying DOX-induced cardiotoxicity. However, existing studies are based on DOX-induced acute or subacute cardiotoxicity model. Therefore, we established a murine model of DOX-induced chronic cardiotoxicity using the clinically relevant cumulative dose, to evaluate the potential molecular mechanism underlying ferroptosis of cardiomycocytes. Male C57 mice were received intraperitoneal injections of DOX at a dose of 3 mg/kg body weight, once a week for 12 weeks. We dynamically analysed echocardiographic findings, serum myocardial enzyme levels, haematological indexes and cardiac histopathological changes. The results showed that, after receiving a cumulative DOX dose of 15 mg/kg, the mice developed anaemia and the function and structure of the heart changed significantly with an increase in the cumulative DOX dose. Importantly, with a cumulative DOX dose of 36 mg/kg, iron overload occurred in the heart tissue. Moreover, RNA-sequencing analysis and experimental verification revealed that ferropotosis is the underlying mechanism of DOX-induced chronic cardiotoxicity. Our results showed that DOX inhibits Slc7a11 in system-Xc, resulting in the reduction of GSH synthesis to prevent GPX4 from scavenging lipid peroxides. In addition, DOX induced the occurrence of ferroptosis via downregulating Nrf2 expression to inhibit HO-1 and GPx4 levels. Our study provides a new perspective for evaluating the pathophysiology of DOX-induced chronic cardiotoxicity in the future, and developing new potential therapeutic strategies for the prevention and treatment of DOX-induced cardiotoxicity.