Astragalus membranaceus (A. membranaceus) is a type of traditional Chinese medicine with a long history of clinical application. It is used in the improvement and treatment of various diseases as medicine and food to invigorate the spleen and replenish qi. The main components of A. membranaceus are Astragalus polysaccharide (APS), flavonoids compounds, saponins compounds, alkaloids, etc. APS is the most important natural active component in A. membranaceus, and possesses multiple pharmacological properties. At present, APS possess the huge potential to develop a drug improving or treating different diseases. In this review, we reveal the potential approaches of pre-treating and preparation on APS as much as possible and the study on content of APS and its chemical composition including different monosaccharides. More importantly, this paper summarize pharmacological actions on immune regulation, such as enhancing the immune organ index, promoting the proliferation of immune cells, stimulating the release of cytokines, and affecting the secretion of immunoglobulin and conduction of immune signals; anti-aging; anti-tumor by enhancing immunity, inducing apoptosis of tumor cells and inhibiting the proliferation and transfer of tumor cells; antiviral effects; regulation of blood glucose such as type I diabetes mellitus, type II diabetes mellitus and diabetic complications; lipid-lowering; anti-fibrosis; antimicrobial activities and anti-radiation. It provided theoretical basis for the further research such as its structure and mechanism of action, and clinical application of APS.

Doxorubicin (DOX), a widely used chemotherapeutic agent, is limited in clinical application due to its dose-dependent cardiotoxicity. Therefore, it is crucial to explore alternative therapeutic molecules or drugs for mitigating DOX-induced cardiomyopathy (DIC). In this study aimed to explore underlying mechanisms of the cardioprotective effects of Kaempferol (KP) against DIC. H9c2 cell-based DIC model were established to explore the pharmacological mechanism. The levels of mitochondrial membrane potential, mitochondrial ROS, mitochondrial Fe²⁺ and lipid peroxidation were detected using JC-1, TMRE, Mito-SOX, Mito-Ferro Green and C11-BODIPY 581/591 probes. Furthermore, Western blot analysis measured the expression of key regulatory proteins, and NRF2-targeting siRNA was transfected into H9c2 cells. The nuclear translocation of NRF2 was assessed by immunofluorescence. Data revealed that KP mitigated DOX-induced mitochondrial damage and ferroptosis via reducing membrane potential, mitochondrial ROS/Fe²⁺, and regulating lipid metabolism. Mechanistically, Western blot analysis revealed that KP inhibited DOX-induced ferroptosis by activating NRF2/SLC7A11/GPX4 axis. Moreover, KP promoted the accumulation and nuclear translocation of NRF2 protein. These findings demonstrated that KP protected against DOX-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis. This provides novel insights into KP as a promising drug candidate for cardioprotection.

Alzheimer's disease (AD)-related brain deterioration is linked to the type 2 diabetes mellitus (T2DM) features hyperglycemia, hyperinsulinemia, and insulin resistance. Hypoxia as a common risk factor for both AD and T2DM. Hypoxia-inducible factor-1 alpha (HIF-1α) acts as the main regulator of the hypoxia response and may be a key target in the comorbidity of AD and T2DM. HIF-1α expression is closely related to hyperglycemia, insulin resistance, and inflammation. Tissue oxygen consumption disrupts HIF-1α homeostasis, leading to increased reactive oxygen species levels and the inhibition of insulin receptor pathway activity, causing neuroinflammation, insulin resistance, abnormal Aβ deposition, and tau hyperphosphorylation. HIF-1α activation also leads to the deposition of Aβ by promoting the abnormal shearing of amyloid precursor protein and inhibiting the degradation of Aβ, and it promotes tau hyperphosphorylation by activating oxidative stress and the activation of astrocytes, which further exasperates AD. Therefore, we believe that HIF-α has great potential as a target for the treatment of AD. Importantly, the intracellular homeostasis of HIF-1α is a more crucial factor than its expression level.

KRAS is a biomarker for non‑small cell lung cancer‑targeted therapy, but there is currently no effective KRAS‑targeting medication. Realgar is an impelling anticancer drug, however its significance in KRAS mutant lung cancer is uncertain. According to our findings, the IC₅₀ of H23 (KRAS mutant) cells is 2.99 times lower than that of H1650 (non‑KRAS mutant) cells. Flow cytometry and the Hoechst 33258 staining assay revealed that H1650 cells treated with 4 µg/ml realgar had an apoptotic rate of 8.2%, while H23 cells had a rate of 21.46%. Accordingly, realgar was more sensitive to KRAS mutant cells. Transcriptome sequencing test indicated that there were 481 different expression genes in H23 cells treated with realgar. In H23 cells treated with realgar, mitochondria shrank, inner membrane folding was disturbed, and mitochondrial membrane potential crushed. Realgar boosted intracellular Fe²⁺, reactive oxygen species, malondialdehyde and glutathione levels, which were all reversed by ferroptosis inhibitor Fer‑1. Realgar decreased phosphorylated p‑Raf, p‑ERK1/2 and increased p‑p38 and p‑JNK, whereas only p‑Raf was abolished by Fer‑1. Raf inhibitor Sorafenib accelerated the realgar‑induced ferroptosis. On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in anti‑KRAS mutant lung cancer.

Shenmai injection is a classic herbal prescription, and is often recommended for the treatment of anthracycline-induced cardiotoxicity. However, the efficacy and safety of Shenmai injection for the treatment of anthracycline-induced cardiotoxicity have not been reported. We conducted a comprehensive search of eight literature databases and two clinical trial registries, retrieving all randomized controlled trials (RCTs) related to the treatment of anthracycline-induced cardiotoxicity with Shenmai injection from the establishment of the databases to July 1, 2023. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. The GRADE pro3.6.1 software was utilized for assessing the quality of evidence. A total of 16 RCTs including 2140 patients were included in this study. Meta-analysis showed that Shenmai injection had an advantage in improving ST-T segment changes (RR = 0.28; 95% CI, 0.20 to 0.39; P < 0.0001) (P < 0.01), creatine kinase isoenzyme (SMD = -3.49; 95% CI, -5.24 to -1.74; P < 0.0001), Prolonged QT interval (RR = 0.46; 95% CI, 0.28 to 0.75; P = 0.0018), Low QRS Voltage (RR = 0.44; 95% CI, 0.27 to 0.71; P = 0.0007), sinus tachycardia (RR = 0.41; 95% CI, 0.28 to 0.60; P < 0.0001), atrial premature beats (RR = 0.55; 95% CI, 0.35 to 0.87; P = 0.01), Premature Ventricular Contractions (RR = 0.39; 95% CI, 0.26 to 0.59; P < 0.0001) and creatine kinase (SMD = -1.43; 95% CI, -2.57 to -0.29; P < 0.0001) in patients with anthracycline-induced cardiotoxicity. advantage, which was supported by sensitivity analyses, but not in improving left ventricular ejection fraction (MD = 16.01; 95% CI, -3.10 to 35.12; P = 0.10) and atrioventricular block (RR = 0.49; 95% CI, 0.24 to 1.03; P = 0.06). The literature included in the study did not refer to data regarding the safety aspects of Shenmai injection, so we do not yet know the safety of Shenmai injection. The results of subgroup analyses suggested that heterogeneity was not related to the administered dose and chemotherapy regimen. The publication bias test showed no publication bias. The quality of evidence for the results ranged from "very low" to "moderate." This study suggests that Shenmai injection is effective in treating anthracycline-induced cardiotoxicity and is a potential treatment for anthracycline-induced cardiotoxicity. However, due to the poor methodological quality of the included RCTs, we recommend rigorous, high-quality, large-sample trials to confirm our findings.