This study explores the mechanisms of Astragaloside A (AS-A), a significant active ingredient in Astragalus, This traditional Chinese medicine is both a medication and a food, combating lung adenocarcinoma using network pharmacology, molecular docking, molecular dynamics, and experimental validation. A protein-protein interaction (PPI) network was developed, identifying 10 key targets, including STAT3 and AKT1. GO and KEGG enrichment analyses indicated that these targets primarily participated in biological processes and pathways, including oxidative stress and the PI3K-Akt signalling pathway. Molecular docking and dynamic simulation evaluated AS-A's binding mode and stability with key targets. In molecular docking, 14 key targets of the HIF-1 signalling pathway had different binding energies with AS-A, such as the binding energy of PIK3R1 being -9.3. Kinetic simulations indicated the stability of the protein-ligand complex, as evidenced by RMSD values ranging from 0.2 to 0.4 nm. RMSF analysis showed that the protein residue flexibility characteristics were stable, the Rg values were stable, the number of hydrogen bonds was 10-20, and the solvent-accessible surface area was stable. Cell experiments showed that AS-A could regulate the expression of key signalling molecules such as STAT3 and AKT in lung adenocarcinoma models. This study provides insights into the mechanism of AS-A in treating lung adenocarcinoma. It proposes a new direction for anticancer research in traditional Chinese medicines, especially medications and foods.

Screening for pulmonary nodules (PN) using low-dose CT has proven effective in reducing lung cancer (LC) mortality. However, current treatments relying on follow-up and surgical excision fail to fully address clinical needs. Pathological angiogenesis plays a pivotal role in supplying oxygen necessary for the progression of PN to LC. The interplay between hypoxia and angiogenesis establishes a vicious cycle, rendering anti-angiogenesis therapy alone insufficient to prevent PN to LC transformation. In traditional Chinese medicine (TCM), PN is referred to as "Feiji," which is mainly attributed to Qi and blood deficiency, correspondingly, the most commonly prescribed medicines are Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (huang qi) (AR) and Angelica sinensis (Oliv.) Diels (dang gui) (ARS). Modern pharmacological studies have demonstrated that AR and ARS possess immune-enhancing, anti-tumor, anti-inflammatory, and anti-angiogenic properties. However, the precise mechanisms through which AR and ARS exert anti-angiogenic effects to delay PN progression to LC remain inadequately understood. This review explores the critical roles of hypoxia and angiogenesis in the transition from PN to LC. It emphasizes that, compared to therapies targeting angiogenic growth factors alone, AR, ARS, and their compound-based prescriptions offer additional benefits. These include ameliorating hypoxia by restoring blood composition, enhancing vascular structure, accelerating circulation, promoting vascular normalization, and blocking or inhibiting various pro-angiogenic expressions and receptor interactions. Collectively, these actions inhibit angiogenesis and delay the PN-to-LC transformation. Finally, this review summarizes recent advancements in related research, identifies existing limitations and gaps in knowledge, and proposes potential strategies and recommendations to address these challenges.

Sentrin/small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) perform pivotal roles in SUMO maturation and recycling, which modulate the balance of SUMOylation/de-SUMOylation and spatiotemporal functions of SUMOylation targets. The malfunction of SENPs often results in cellular dysfunction and various diseases. However, studies rarely investigated the correlation between SENP2 and lung cancer. This study revealed that SENP2 is a required contributor to lung cancer-cell growth and targets nuclear Dbf2-related 2 (NDR2, also known as serine/threonine kinase 38L or STK38L) for de-SUMOylation, which improves NDR2 kinase activity. This condition leads to the instability of downstream target p21 in accelerating the G1/S cell cycle transition and suggests SENP2 as a promising therapeutic target for lung cancer in the future. Specifically, astragaloside IV, an active ingredient of Jinfukang Oral Liquid (JOL, a clinical combination antilung cancer drug approved by the National Food and Drug Administration (FDA) of China), can repress lung cancer-cell growth via the SENP2-NDR2-p21 axis, which provides new insights into the molecular mechanism of JOL for lung cancer treatment.

Drug resistance of malignant tumor leads to disease progression be the bottleneck in clinical treatment. Antiangiogenic therapy, which aims to "starve" the tumor by inhibiting angiogenesis, is one of the key strategies in clinical oncology treatments. Recently, dozens of investigational antibody drugs and biosimilars targeting angiogenesis have obtained regulatory approval for the treatment of various malignancies. Moreover, a new generation of bispecific antibodies based on the principle of antiangiogenesis are being advanced for clinical trial to overcome antiangiogenic resistance in tumor treatment or enhance the efficacy of monotherapy. Tumors often develop resistance to antiangiogenesis therapy, presenting as refractory and sometimes even resistant to new therapies, for which there are currently no effective management strategies. Thus, a detailed understanding of the mechanisms mediating resistance to antiangiogenesis antibodies is crucial for improving drug effectiveness and achieving a durable response to antiangiogenic therapy. In this review, we provide a novel perspective on the tumor microenvironment, including antibody structure, tumor stroma, and changes within tumor cells, to analyze the multifactorial reasons underlying resistance to antiangiogenesis antibodies. The review also enumerates biomarkers that indicate resistance and potential strategies for monitoring resistance. Furthermore, based on recent clinical and preclinical studies, we summarize potential strategies and translational clinical trials aimed at overcoming resistance to antiangiogenesis antibodies. This review provides a valuable reference for researchers and clinical practitioners involved in the development of new drugs or therapeutic strategies to overcome antiangiogenesis antibodies resistance.

Autophagy and endoplasmic reticulum (ER) stress are conserved processes that generally promote survival, but can induce cell death when physiological thresholds are crossed. The pro-survival aspects of these processes are exploited by cancer cells for tumor development and progression. Therefore, anticancer drugs targeting autophagy or ER stress to induce cell death and/or block the pro-survival aspects are being investigated extensively. Consistently, several phytochemicals have been reported to exert their anticancer effects by modulating autophagy and/or ER stress. Various phytochemicals (e.g., celastrol, curcumin, emodin, resveratrol, among others) activate the unfolded protein response to induce ER stress-mediated apoptosis through different pathways. Similarly, various phytochemicals induce autophagy through different mechanisms (namely mechanistic target of Rapamycin [mTOR] inhibition). However, phytochemical-induced autophagy can function either as a cytoprotective mechanism or as programmed cell death type II. Interestingly, at times, the same phytochemical (e.g., 6-gingerol, emodin, shikonin, among others) can induce cytoprotective autophagy or programmed cell death type II depending on cellular contexts, such as cancer type. Although there is well-documented mechanistic interplay between autophagy and ER stress, only a one-way modulation was noted with some phytochemicals (carnosol, capsaicin, cryptotanshinone, guangsangon E, kaempferol, and δ-tocotrienol): ER stress-dependent autophagy. Plant extracts are sources of potent phytochemicals and while numerous phytochemicals have been investigated in preclinical and clinical studies, the search for novel phytochemicals with anticancer effects is ongoing from plant extracts used in traditional medicine (e.g., Origanum majorana). Nonetheless, the clinical translation of phytochemicals, a promising avenue for cancer therapeutics, is hindered by several limitations that need to be addressed in future studies.

The rising global morbidity and mortality rates of non-small cell lung cancer (NSCLC) underscore the urgent need for more effective treatments. Current therapeutic modalities-including surgery, radiotherapy, chemotherapy, and targeted therapy-face several limitations. Recently, Astragalus membranaceus, a traditional Chinese medicine (TCM), has captured significant attention due to its broad pharmacological properties, such as immune regulation, anti-inflammatory effects, and the modulation of reactive oxygen species (ROS) and enzyme activities. This review delivers a comprehensive summary of the most recent advancements and ongoing applications of Astragalus membranaceus in NSCLC treatment, underlining its potential for integration into existing treatment protocols. It also highlights essential areas for future research, including the elucidation of its molecular mechanisms, optimization of dosage and administration, and evaluation of its efficacy and safety alongside standard therapies, all of which could potentially improve therapeutic outcomes for NSCLC patients.

Astragalus membranaceus saponins are the main components of A. membranaceus, a plant widely used in traditional Chinese medicine. Recently, research on the anti-cancer effects of A. membranaceus saponins has received increasing attention. Numerous in vitro and in vivo experimental data indicate that A. membranaceus saponins exhibit significant anti-cancer effects through multiple mechanisms, especially in inhibiting tumor cell proliferation, migration, invasion, and induction of apoptosis, etc. This review compiles relevant studies on the anti-cancer properties of A. membranaceus saponins from various databases over the past two decades. It introduces the mechanism of action of astragalosides, highlighting their therapeutic benefits in the management of cancer. Finally, the urgent problems in the research process are highlighted to promote A. membranaceus saponins as an effective drug against cancer.

Malignant tumors are complex systemic chronic diseases and one of the major causes of human mortality. Targeted therapy, chemotherapy, immunotherapy, and radiotherapy are examples of mainstream allopathic medicine treatments that effective for intermediate and advanced malignant tumors. The ongoing use of conventional allopathic medicine has resulted in adverse responses and drug resistance, which have hampered its efficacy. As an important component of complementary and alternative medicine, Chinese medicine has been found to have antitumor effects and has played an important role in enhancing the therapeutic sensitivity of mainstream allopathic medicine, reducing the incidence of adverse events and improving immune-related functions. The combined application of adjuvant Chinese medicine and mainstream allopathic medicine has begun to gain acceptance and is gradually used in the field of antitumor therapy. Traditional natural medicines and their active ingredients, as well as Chinese patent medicines, have been proven to have excellent therapeutic efficacy and good safety in the treatment of various malignant tumors. This paper focuses on the mechanism of action and research progress of combining the above drugs with mainstream allopathic medicine to increase therapeutic sensitivity, alleviate drug resistance, reduce adverse reactions, and improve the body's immune function. To encourage the clinical development and use of Chinese herb adjuvant therapy as well as to provide ideas and information for creating safer and more effective anticancer medication combinations, the significant functions of Chinese herb therapies as adjuvant therapies for cancer treatment are described in detail.

Astragaloside IV has emerged as a pharmaceutical monomer with great medical applications and potential. Astragaloside IV has many effects such as improving myocardial ischemia, cerebral ischemia-reperfusion injury, anti-inflammatory, analgesic, antiviral, promoting lymphocyte proliferation, and antitumor effects. However, there are few bibliometric studies on astragaloside IV.

We aim to visualize the hotspots and trends in astragaloside IV research through bibliometric analysis to further understand the future development of basic and clinical research. Methods The articles and reviews on astragaloside IV were screened from the Web of Science Core Collection, and knowledge maps were generated using CiteSpace software. Bibliometric analysis was performed on 971 articles published from 1998 to 2022.

The number of articles on astragaloside IV increased yearly. These publications came from 42 countries/regions, with China being the largest. The primary research institutions were Shanghai University of Traditional Chinese Medicine and Guangzhou University of Traditional Chinese Medicine. Journal of Ethnopharmacology was the most studied journal and co-cited journal. A total of 473 authors were included, among which Hongxin Wang had the highest number of publications and Zhang Wd had the highest total citation frequency. After analysis, the most common keywords are astragaloside IV, expression, and oxidative stress. Cardiovascular disease, cerebral ischemia, cancer, and kidney disease are current and developing research fields.

This study used bibliometrics and visualization methods to analyze the research hotspots and trends of astragaloside IV. Astragaloside IV on ischemia-reperfusion injury, cancer, and tumor may become the focus of future research.

With the increasing prevalence of hypertension, diabetes, and obesity, the incidence of kidney diseases is also increasing, resulting in a serious public burden. Conventional treatments for kidney diseases have unsatisfactory effects and are associated with adverse reactions. Traditional Chinese medicines have good curative effects and advantages over conventional treatments for preventing and treating kidney diseases. Astragali Radix is a Chinese herbal medicine widely used to treat kidney diseases.

To review the potential applications and molecular mechanisms underlying the renal protective effects of Astragali Radix and its components and to provide direction and reference for new therapeutic strategies and future research and development of Astragali Radix.

PubMed, Google Scholar, and Web of Science were searched using keywords, including "Astragali Radix," "Astragalus," "Astragaloside IV" (AS-IV), "Astragali Radix polysaccharide" (APS), and "kidney diseases." Reports on the effects of Astragali Radix and its components on kidney diseases were identified and reviewed.

The main components of Astragali Radix with kidney-protective properties include AS-IV, APS, calycosin, formononetin, and hederagenin. Astragali Radix and its active components have potential pharmacological effects for the treatment of kidney diseases, including acute kidney injury, diabetic nephropathy, hypertensive renal damage, chronic glomerulonephritis, and kidney stones. The pharmacological effects of Astragali Radix are manifested through the inhibition of inflammation, oxidative stress, fibrosis, endoplasmic reticulum stress, apoptosis, and ferroptosis, as well as the regulation of autophagy.

Astragali Radix is a promising drug candidate for treating kidney diseases. However, current research is limited to animal and cell studies, underscoring the need for further verifications using high-quality clinical data.

Respiratory diseases are an emerging public health concern, that pose a risk to the global community. There, it is essential to establish effective treatments to reduce the global burden of respiratory diseases. Astragaloside IV (AS-IV) is a natural saponin isolated from Radix astragali (Huangqi in Chinese) used for thousands of years in Chinese medicine. This compound has become increasingly popular due to its potential anti-inflammatory, antioxidant, and anticancer properties. In the last decade, accumulated evidence has indicated the AS-IV protective effect against respiratory diseases. This article presents a current understanding of AS-IV roles and mechanisms in combatting respiratory diseases. The ability of the agent to suppress oxidative stress, cell proliferation, and epithelial-mesenchymal transition (EMT), to attenuate inflammatory responses, and modulate programmed cell death (PCD) will be discussed. This review highlights the current challenges in respiratory diseases and recommendations to improve disease management.

One of the most important and effective components of Astragalus membranaceus is astragaloside IV (AS-IV), which can exert anti-tumor effects through various pathways. For instance, AS-IV exerts an anti-tumor effect by acting at the cellular level, regulating the phenotype switch of tumor-associated macrophages, or inhibiting the development of tumor cells. Furthermore, AS-IV inhibits tumor cell progression by enhancing its sensitivity to antitumor drugs or reversing the drug resistance of tumor cells. This article reviews the different mechanisms of AS-IV inhibition of epithelial-mesenchymal transition (EMT), migration, proliferation, and invasion of tumor cells, inducing apoptosis and improving the sensitivity of anti-tumor drugs. This review summarizes recent progress in the current research into AS-IV anti-tumor effect and provides insight on the next anti-tumor research of AS-IV.

Cancer is a global intractable disease, and its morbidity and mortality are increasing year by year in developing countries. Surgery and chemotherapy are often used to treat cancer, but they result in unsatisfactory outcomes, such as severe side effects and drug resistance. With the accelerated modernization of traditional Chinese medicine (TCM), an increasing body of evidence has shown that several TCM components have significant anticancer activities. Astragaloside IV (AS-IV) is considered the main active ingredient of the dried root of Astragalus membranaceus. AS-IV exhibits various pharmacological effects, such as anti-inflammatory, hypoglycemic, antifibrotic, and anticancer activities. AS-IV possesses a wide range of activities, such as the modulation of reactive oxygen species-scavenging enzyme activities, participation in cell cycle arrest, induction of apoptosis and autophagy, and suppression of cancer cell proliferation, invasiveness, and metastasis. These effects are involved in the inhibition of different malignant tumors, such as lung, liver, breast, and gastric cancers. This article reviews the bioavailability, anticancer activity, and mechanism of AS-IV and provides suggestions for further research of this TCM.