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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.

Interleukin-33 (IL-33) is a nuclear factor and member of the IL-1 cytokine family. IL-33 is mainly expressed by epithelial and endothelial cells and exerts its function through interaction with various immune cells, and binding to its receptor can form the IL-33/Suppression of tumorigenicity 2 (ST2) signaling pathway. While most cytokines are actively synthesized within cells, IL-33 is produced passively in response to tissue damage or cell necrosis, indicating its role as a signaling molecule following cellular infection, stress, or trauma. IL-33/ST2 signaling pathway has been proved to play diverse role in the pathological process of central nervous system disorders, cancer, fibrosis, autoimmune diseases, etc. Although research on the IL-33/ST2 signaling pathway has deepened recently, relevant treatment strategies have been proposed, and even targeted drugs are in the preclinical stage; further research on the effect of the IL-33/ST2 signaling pathway in different diseases is still necessary, to provide a clearer understanding of the different roles of IL-33/ST2 in disease progression and to develop new drugs and treatment strategies. Because IL-33/ST2 plays an important role in the occurrence and progression of diseases, the study of therapeutic drugs targeting this pathway is also necessary. This review focused on recent studies on the positive or negative role of IL-33/ST2 in different diseases, as well as the current related drugs targeting IL-33/ST2 in the preclinical and clinical stage. The mechanism of IL-33/ST2 in different diseases and its mediating effect on different immune cells have been summarized, as well as the antibody drugs targeting IL-33 or ST2, natural compounds with a mediating effect, and small molecule substances targeting relative pathway. We aim to provide new ideas and treatment strategies for IL-33/ST2-related drugs to treat different diseases.

Fagopyrum dibotrys ( F. dibotrys ) (D.Don) H.Hara is a well-known edible herbal medicine in Asian countries. It has been widely used for the treatment of lung diseases, swelling, etc., and is also an important part of many Chinese medicine prescriptions. At present, more than 100 compounds have been isolated and identified from F. dibotrys , and these compounds can be primarily divided into flavonoids, phenols, terpenes, steroids, and fatty acids. Flavonoids and phenolic compounds are considered to be the main active ingredients of F. dibotrys . Previous pharmacological studies have shown that F. dibotrys possesses anti-inflammatory, anti-cancer, anti-oxidant, anti-bacterial, and anti-diabetic activities. Additional studies on functional genes have led to a better understanding of the metabolic pathways and regulatory factors related with the flavonoid active ingredients in F. dibotrys . In this paper, we systemically reviewed the research advances on the phytochemistry and pharmacology of F. dibotrys , as well as the functional genes related to the synthesis of active ingredients, aiming to promote the development and utilization of F. dibotrys .

Age-related macular degeneration (AMD) represents a predominant cause of blindness among older adults, with limited therapeutic options currently available. Oxidative stress, inflammation, and retinal pigment epithelium injury are recognized as key contributors to the pathogenesis of AMD. Regulated cell death plays a pivotal role in mediating cellular responses to stress, maintaining tissue homeostasis, and contributing to disease progression. Recent research has elucidated several regulated cell death pathways—such as apoptosis, ferroptosis, pyroptosis, necroptosis, and autophagy—that may contribute to the progression of AMD owing to cell death in the retinal pigment epithelium. These discoveries open new avenues for therapeutic interventions in patients with AMD. In this review, we provide a comprehensive summary and analysis of the latest advancements regarding the relationship between regulated cell death and AMD. Moreover, we examined the therapeutic potential of targeting regulated cell death pathways for the treatment and prevention of AMD, highlighting their roles as promising targets for future therapeutic strategies. [Display omitted] •Age-related macular degeneration (AMD) has currently limited therapeutic options.•So far, the role of regulated cell death in AMD pathology has been neglected.•Apoptosis, ferroptosis, pyroptosis, necroptosis, and autophagy contribute to AMD.•Key elements in their pathways are promising therapeutic targets in AMD.

Introduction: The current quality evaluation of traditional Chinese medicine (TCM) is difficult to attribute to clinical efficacy due to the complexity of TCM. Zishen Yutai pill (ZYP), a well-known traditional Chinese patent medicine, has been widely used to prevent recurrent miscarriage and treat threatened abortion. However, the chemical components of ZYP are unknown, and there is no convincing quality control method applied on ZYP. Although ZYP has been found to promote endometrial receptivity and treat impending abortion, the substantial basis of the therapeutic effects is unclear. The aim of this study was to clarify the quality markers correlated with the potential medicinal activities and provide a theoretical foundation for scientific quality control and product quality improvement of ZYP. Methods: The chemical constituents of ZYP were comprehensively analyzed by offline two-dimensional liquid chromatography-mass spectrometry (2DLC-LTQ-Orbitrap-MS). The efficacy of the 27 ZYP orthogonal groups was investigated using the HTR-8/SVneo oxidative damage model and migration model in vitro , as well as the endometrial receptivity disorder mouse model and premature ovarian failure mouse model in vivo . Based on the efficacy and mass spectral results, spectrum–effect relationship analysis was used to identify the chemical components with corresponding pharmacological activities. Results: A total of 589 chemical components were found in ZYP, of which 139 were not identified in the literature. The potential quality markers for ZYP were successfully identified through orthogonal design and spectrum–effect relationship analysis. By combining mass spectrum data and pharmacological results of 27 orthogonal groups, 39 substances were identified as potential quality markers. Conclusion: The approaches used in this study will provide a feasible strategy for the discovery of quality markers with bioactivity and further investigation into the quality evaluation of TCM.

Approximately 30% of epileptic patients worldwide are medically unable to control their seizures. In addition, repeated epileptic seizures generally lead to neural damage. Pentylenetetrazol (PTZ) is a clinical circulatory and respiratory stimulant that is experimentally used to mimic epileptic convulsion in epilepsy research. Here, we systematically explore the neuroprotective effects of a pure compound isolated from Cynanchum otophyllum Schneid (Qingyangshen), Otophylloside N (OtoN), against PTZ-induced neuronal injury. We used three models: in vitro primary cortical neurons, in vivo mice, and in vivo zebrafish. Our results revealed that OtoN treatment may attenuate PTZ-induced morphology changes, cell death, LDH efflux in embryonic neuronal cells of C57BL/6J mice, and convulsive behavior in zebrafish. Additionally, our Western blot and RT-PCR results demonstrated that OtoN may attenuate PTZ-induced apoptosis and neuronal activation in neuronal cells, mice, and zebrafish. OtoN may reduce PTZ-induced cleavage of poly ADP-ribose polymerase and upregulation of the Bax/Bcl-2 ratio and decrease the expression level of c-Fos. This study is the first investigation of the neuroprotective effects of OtoN, which might be developed as a novel antiepileptic drug.

Microglia mediated neuronal inflammation has been widely reported to be responsible for neurodegenerative disease. Deacetyl ganoderic acid F (DeGA F) is a triterpenoid isolated from Ganoderma lucidum, which is a famous edible and medicinal mushroom used for treatment of dizziness and insomnia in traditional medicine for a long time. In this study the inhibitory effects and mechanisms of DeGA F against lipopolysaccharide (LPS)-induced inflammation both in vitro and in vivo were investigated. On murine microglial cell line BV-2 cells, DeGA F treatment inhibited LPS-triggered NO production and iNOS expression and affected the secretion and mRNA levels of relative inflammatory cytokines. DeGA F inhibited LPS-induced activation of the NF-κB pathway, as evidenced by decreased phosphorylation of IKK and IκB and the nuclear translocation of P65. In vivo, DeGA F treatment effectively inhibited NO production in zebrafish embryos. Moreover, DeGA F suppressed the serum levels of pro-inflammatory cytokines, including TNF-α and IL-6 in LPS-stimulated mice model. DeGA F reduced inflammatory response by suppressing microglia and astrocytes activation and also suppressed LPS-induced NF-κB activation in mice brains. Taken together, DeGA F exhibited remarkable anti-inflammatory effects and promising therapeutic potential for neural inflammation associated diseases.

Ganoderma Lingzhi, which is called “Lingzhi” in Chinese, is fungi that belong to polyproraceae Ganoderma. Many species of fungi are called Lingzhi, but only the Ganoderma lucidum (Ley-ss.ex Fr.) Karst., Ganoderma sinense Zhao, Xu et Zhang are authorized as the herbal sources for clinical use according to Chinese Pharmacopeia record. Lingzhi is a famous herbal medicine and edible mushroom and is assorted into class of “superior herb” since it is absolutely safe without any side effects for long-term use. In traditional Chinese medicine, Lingzhi was often applied in treatment of ahypnosis, palpitate, neurasthenia, dizziness, and insomnia. Modern pharmacological research reported that Lingzhi possesses anti-tumor, anti-hypertensive, hepatoprotective and antioxidant effects, as well as anti-inflammation and immunomodulation activities. And recently, the benefits of Lingzhi for neurodegenerative diseases also have been well demonstrated at different levels. For instance, extract from Lingzhi was indicated being able to enhance learning memory and cognitive function, alleviate dementia and insomnia. In this thesis, we tried to explore the potential ingredients for the treatment of neurodegenerative diseases from Lingzhi, as well as the underlying mechanisms.Firstly, the chemical profile of Lingzhi has been systematically investigated. For the aqueous extract of Lingzhi, a MECK method was established to determine the content of ten nucleosides and bases, including cytosine, hypoxanthine, adenine, guanine, guanosine, adenosine, uracil, thymine, cytidine, and uridine. And according to followed PCA and HCA analysis, the geographical origin is suggested as a significant factor affecting the accumulation of nucleosides and bases in Lingzhi. For the alcohol extract of Lingzhi, a UPLC LTQ-Orbitrap method was established to apply for constitute analysis. Based on the fragmental pattern and further comparison with reference standards and data from reference paper reports, totally 40 compounds in the extract were identified or tentatively speculated by the established method. The results provide a reliable reference for quality control and further study of Lingzhi.Then, based on network pharmacology, 43 candidate compounds and 137 intersected targets were retrieved and then took into the following analysis. The results from GO and KEGG enrichment indicated that a serious of targets and mechanisms regarding immunoregulation were deduced to contribute to the therapeutic effect of Lingzhi on neurodegenerative disease. The results of verified test further confirmed that Lingzhi could enhance phagocytosis of macrophage in LPS-triggered carbon clearance model in vivo and inhibit the production of inflammatory cytokines in LPS-stimulated macrophage in vitro, which partially validated the outcomes from network pharmacology.In the last section, we demonstrated that Deacetyl ganoderic acid F (DeGA F), a Ganoderma acid from Lingzhi, inhibited LPS stimulated inflammatory response in BV-2 cells as evidenced by the suppression of NO production and pro-inflammatory cytokines secretion. Modulation of the NF-κB pathway may be a dominant mechanism underlying the anti-inflammatory effects of DeGA F. In addition, DeGA F suppressed NO production in LPS stimulated zebrafish model and inhibited the serum levels of pro-inflammatory cytokines TNF-α and IL-6 in LPS stimulated mice model. DeGA F reduced inflammatory response by suppressing microglia and astrocytes activation and also suppressed LPS-induced NF-κB activation in mice brain. This study provided evidence for the therapeutic potential of DeGA F in neural inflammation associated diseases.Taken together, in this thesis we investigated the chemical profile of Lingzhi, then predicted the potential active compounds and key mechanisms of Lingzhi for the treatment of neurodegenerative diseases by using network pharmacology analysis, and finally revealed the anti-inflammatory effects and associated mechanism of DeGA F, which well verified the results by network pharmacology analysis. This thesis provided evidence for the potential therapeutic effects of DeGA F in neural inflammation related diseases.

Herbal injection is one of the most important preparations of traditional Chinese medicine. More than 130 types of herbal injections are used clinically for 400 million patients annually with total sales of over four billion US dollars per year. However, the current quality control (QC) methods relying mainly on chemical fingerprints (CF) can hardly ensure quality and safety of the herbal injections with complex chemical composition and have resulted in an increase in serious adverse drug reactions. In this study, a comprehensive approach for the QC of a controversial herbal injection Shuang-Huang-Lian lyophilized powder (SHL) was established based on the quality fluctuation detection by a combination of CF and biological fingerprint (BF). High-performance liquid chromatography and the impedance-based xCELLigence system were applied to establish the CF and BF, respectively. In addition, multivariate analysis was performed to evaluate the discriminant ability of the two methods. The results showed that being subjected to environmental influence like oxygen/air, high temperature, and extreme illumination could lead to quality fluctuation of SHL. The combination of chemical and biological fingerprint method is a more powerful tool for the QC of SHL because it can clearly discriminate different groups of abnormal samples. This method can be used for the detection of quality fluctuation of SHL and can provide reference for the quality control of other herbal injections.