Asperuloside regulates the proliferation, apoptosis, and differentiation of chronic myeloid leukemia cell line K562 through the RAS/MEK/ERK pathway.

Context: Chronic myeloid leukemia (CML) is a malignant hematopoietic stem cell disease caused by excessive proliferation and abnormal differentiation of hematopoietic stem cells. Asperuloside (ASP) is considered to have good biological activity and may be a good anti-CML drug. Objective: This study aimed to explore the effects and possible mechanisms of ASP on the biological behavior of K562 cells based on RNA-seq. Materials and methods: The IC50 of ASP in K562 cells was calculated by the concentration-effect curve. Cell viability, apoptosis, and differentiation were detected by CCK8, flow cytometry, benzidine staining, and WB analysis, respectively. Further, RNA-seq was used to analyze the possible mechanism of ASP regulating K562 cells. Results: ASP significantly inhibited the proliferation, and promoted apoptosis and differentiation of K562 cells. A total of 117 differentially expressed genes were screened by RNA-seq, mainly involved in the RAS/MEK/ERK pathway. PD98059 was used to inhibit the RAS/MEK/ERK pathway in K562 cells, and results confirmed that PD98059 could not only inhibit the RAS/MEK/ERK pathway, but also inhibit the regulation of ASP on the proliferation and differentiation of K562 cells. Conclusion: ASP inhibited the proliferation, promoted apoptosis and differentiation of K562 cells by regulating the RAS/MEK/ERK pathway, and played a good anti-CML role.

Research Progress on Traditional Chinese Medicine in Treating Viral Hepatitis： A Review / 中国实验方剂学杂志

Viral hepatitis is an important cause of liver cirrhosis and liver cancer， which has become a major public health problem in the world. Traditional Chinese medicine has unique advantages in treating viral hepatitis， which can inhibit virus replication and enhance immunity. It can effectively prevent liver fibrosis and canceration， improving liver function and symptoms significantly with definite clinical curative effects， a high level of safety， and seldom drug resistance. In addition， it reduces the side effects of western medicine， achieving the effect of synergy and attenuation while reducing the recurrence rate of patients after drug withdrawal. Attention has been paid to the research on the treatment of viral hepatitis with traditional Chinese medicine， and great progress has been made in experimental research and clinical practice. In this paper， the research progress of traditional Chinese medicine in the treatment of viral hepatitis at home and abroad in recent five years was systematically reviewed. Modern research has confirmed that traditional Chinese medicine can play a role in the treatment of viral hepatitis by directly or indirectly inhibiting the virus， anti-inflammatory， anti-fibrosis， anti-oxidation， regulating immunity， regulating autophagy， and other signal pathways. In clinics， traditional Chinese medicine compound or combined with western medicine is often adopted to ameliorate the clinical symptoms of patients such as fatigue and loss of appetite， improve the immune mechanism of the body， enhance the antiviral ability， shorten the treatment course of patients and improve their quality of life. The research provides a reference for pharmacological research， clinical research， and new drug development for viral hepatitis.

Artificial Intelligence and Machine Learning in Pharmacological Research: Bridging the Gap Between Data and Drug Discovery.

Artificial intelligence (AI) has transformed pharmacological research through machine learning, deep learning, and natural language processing. These advancements have greatly influenced drug discovery, development, and precision medicine. AI algorithms analyze vast biomedical data identifying potential drug targets, predicting efficacy, and optimizing lead compounds. AI has diverse applications in pharmacological research, including target identification, drug repurposing, virtual screening, de novo drug design, toxicity prediction, and personalized medicine. AI improves patient selection, trial design, and real-time data analysis in clinical trials, leading to enhanced safety and efficacy outcomes. Post-marketing surveillance utilizes AI-based systems to monitor adverse events, detect drug interactions, and support pharmacovigilance efforts. Machine learning models extract patterns from complex datasets, enabling accurate predictions and informed decision-making, thus accelerating drug discovery. Deep learning, specifically convolutional neural networks (CNN), excels in image analysis, aiding biomarker identification and optimizing drug formulation. Natural language processing facilitates the mining and analysis of scientific literature, unlocking valuable insights and information. However, the adoption of AI in pharmacological research raises ethical considerations. Ensuring data privacy and security, addressing algorithm bias and transparency, obtaining informed consent, and maintaining human oversight in decision-making are crucial ethical concerns. The responsible deployment of AI necessitates robust frameworks and regulations. The future of AI in pharmacological research is promising, with integration with emerging technologies like genomics, proteomics, and metabolomics offering the potential for personalized medicine and targeted therapies. Collaboration among academia, industry, and regulatory bodies is essential for the ethical implementation of AI in drug discovery and development. Continuous research and development in AI techniques and comprehensive training programs will empower scientists and healthcare professionals to fully exploit AI's potential, leading to improved patient outcomes and innovative pharmacological interventions.

[The fight against antibiotic resistance: what does the future hold?] / Lutte contre l'antibiorésistance, quelles perspectives d'avenir ?

The fight against antibiotic resistance is faced with a lack of therapeutic innovation, due to the low return on investment for players in the pharmaceutical sector. Research challenges need to integrate a translational research strategy for the development of new therapeutics in a One Health approach. For synergistic collaboration, public-private partnerships have been set up with financial support mechanisms for the marketing of new anti-infectives, enabling a return on investment for players in the pharmaceutical sector.

Potential application of Atractylodes macrocephala Koidz. as a natural drug for bone mass regulation: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Atractylodes macrocephala Koidz. (AM) has been used for thousands of years in China, and it's extracts contain various constituents, such as volatile oils, polysaccharides, and lactones, with a myriad of pharmacological effects, including improves the healthy state of the gastrointestinal system and regulating immunity, hormone secretion, anti-inflammatory, antibacterial, antioxidation, anti-aging, and antitumor properties. Recently, researchers have focused on the effect of AM in regulating bone mass; therefore, its potential mechanism of action in regulating bone mass needs to be elucidated. AIM OF REVIEW: This study reviewed the known and possible mechanisms of bone mass regulation by AM. MATERIALS AND METHODS: Cochrane, Medline via PubMed, Embase, CENTRAL, CINAHL, Web of Science, Chinese biomedical literature database, Chinese Science and Technology Periodical Database, and Wanfang Database were used to search AM root extracts-related studies. The retrieval date was from the establishment of the database to January 1, 2023. RESULTS: By summarizing 119 natural active substances that have been isolated from AM root to date, we explored its possible targets and pathways (such as Hedgehog, Wnt/ß-catenin, and BMP/Smads pathways etc.) for bone growth and presented our position on possible future research/perspectives in the regulation of bone mass using this plant. CONCLUSIONS: AM root extracts (incuding aqueous, ethanol etc.) promotes osteogenesis and inhibits osteoclastogenesis. These functions promote the absorption of nutrients, regulate gastrointestinal motility and intestinal microbial ecology, regulate endocrine function, strengthen bone immunity, and exert anti-inflammatory and antioxidant effects.

Utilisation of Chick Embryo Chorioallantoic Membrane as a Model Platform for Imaging-Navigated Biomedical Research.

The fertilised chick egg and particularly its chorioallantoic membrane (CAM) have drawn continuing interest in biomedicine and bioengineering fields, especially for research on vascular study, cancer, drug screening and development, cell factors, stem cells, etc. This literature review systemically introduces the CAM's structural evolution, functions, vascular features and the circulation system, and cell regulatory factors. It also presents the major and updated applications of the CAM in assays for pharmacokinetics and biodistribution, drug efficacy and toxicology testing/screening in preclinical pharmacological research. The time course of CAM applications for different assays and their advantages and limitations are summarised. Among these applications, two aspects are emphasised: (1) potential utility of the CAM for preclinical studies on vascular-disrupting agents (VDAs), promising for anti-cancer vascular-targeted therapy, and (2) modern imaging technologies, including modalities and their applications for real-time visualisation, monitoring and evaluation of the changes in CAM vasculature as well as the interactions occurring after introducing the tested medical, pharmaceutical and biological agents into the system. The aim of this article is to help those working in the biomedical field to familiarise themselves with the chick embryo CAM as an alternative platform and to utilise it to design and optimise experimental settings for their specific research topics.

Research Progress in Pharmacology of Xiaoyaowan / 中国实验方剂学杂志

In traditional Chinese medicine， it is believed that the spleen is the foundation of acquired nature and the source of Qi and blood. All life activities of a person since birth depend on the water and grain essence transported by spleen and stomach. The liver helps the spleen to strengthen the movement， the liver and spleen cooperate with each other. The liver and the spleen are invigorated， so that the Qi and blood are sufficient. The external energy can nourish the limbs， muscles and fur. The Qi and blood can be supplied to the internal organs， meridians and bones， and the body can be nourished both inside and outside to strengthen the acquired foundation. Emotional dissatisfaction can lead to stagnation of liver Qi， loss of spleen Qi， failure to dredge Qi， and deficiency of spleen Qi， forming the syndrome of liver depression and spleen deficiency. Its clinical manifestations include the symptoms of liver Qi stagnation such as depression， stamina， and chest fullness， as well as symptoms of spleen deficiency such as anorexia， abdominal distension， loose stools. Xiaoyaowan is an effective classic prescription for the treatment of liver stagnation and spleen deficiency syndrome， which is based on the dosage form of Xiaoyaosan in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy. It has the effect of relieving depression， nourishing blood and invigorating spleen. In modern research， it has been found that Xiaoyaowan has good curative effect in the treatment of endocrine diseases， liver diseases， immune diseases， and neurological diseases， etc. It was praised by the famous medical scientist YE Tian-shi in the Qing Dynasty as "the holy medicine for women"， with a wide range of significant curative effects gynecology. Progress has been also made in pharmacological research. In this article， we have searched and consulted the relevant literature reports of Xiaoyaowan in recent years， summarized the key directions of the pharmacological research literature， and proposed deficiencies to provide relevant basis for the in-depth study of Xiaoyao pill in the future.

Identification of the active compounds and drug targets of Chinese medicine in heart failure based on the PPARs-RXRα pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Danqi Pill (DQP), commonly known as a routinely prescribed traditional Chinese medicine (TCM), is composed of Salviae Miltiorrhizae Radix et Rhizoma and Notoginseng Radix et Rhizoma and effective in treating heart failure (HF) clinically due to their multicompound and multitarget properties. However, the exact active compounds and corresponding targets of DQP are still unknown. AIM OF THE STUDY: This study aimed to investigate active compounds and drug targets of DQP in heart failure based on the PPARs-RXRα pathway. MATERIALS AND METHODS: Network pharmacology was used to predict the compound-target interactions of DQP. Left anterior descending (LAD)-induced HF mouse model and oxygen-glucose deprivation/recovery (OGD/R)-induced H9C2 model were constructed to screen the active compounds of DQP. RESULTS: According to BATMAN-TCM (a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine we previously developed), 24 compounds in DQP were significantly enriched in the peroxisome proliferator activated receptors-retinoid X receptor α (PPARs-RXRα) pathway. Among them, Ginsenoside Rb3 (G-Rb3) had the best pharmacodynamics against OGD/R-induced loss of cell viability, and it was selected to verify the compound-target interaction. In HF mice, G-Rb3 protected cardiac functions and activated the PPARs-RXRα pathway. In vitro, G-Rb3 protected against OGD/R-induced reactive oxygen species (ROS) production, promoted the expressions of RXRα and sirtuin 3 (SIRT3), thereafter improved the intracellular adenosine triphosphate (ATP) level. Immunofluorescent staining demonstrated that G-Rb3 could activate RXRα, and facilitate RXRα shifting to the nucleus. HX531, the specific inhibitor of RXRα, could abolish the protective effects of G-Rb3 on RXRα translocation. Consistently, the effect was also confirmed on RXRα siRNA cardiomyocytes model. Moreover, surface plasmon resonance (SPR) assays identified that G-Rb3 bound directly to RXRα with the affinity of KD = 10 × 10-5 M. CONCLUSION: By integrating network pharmacology and experimental validation, we identified that as the major active compound of DQP, G-Rb3 could ameliorate ROS-induced energetic metabolism dysfunction, maintain mitochondrial function and facilitate energy metabolism via directly targeting on RXRα. This study provides a promising strategy to dissect the effective patterns for TCM and finally promote the modernization of TCM.

The Status quo and way forwards on the development of Tibetan medicine and the pharmacological research of tibetan materia Medica.

Tibetan medicine (TM), the second largest traditional Chinese medicine system in China, boasts a long history and an integrated theoretical system. It abounds with classical medical works constituing a unique corpus of Tibetan materia medica (TMM). China has now conceived a modern education system of TM, and Tibetan medical hospitals at different levels have been set up. Many enterprises are granted the privileges to produce preparations of TM in compliance with Good Manufacturing Practices (GMP) regulations. However, there still exist unsolved issuess in TMM research as to the mechanism of action and the active constituents of TMM which are now been tackled through pharmacology and modern science and technology. Up till now, the mechanism of action and the active constituents of 141 medicines as well as 230 preparations of TM have been preliminarily revealed. This paper reviews in detail the development of TM and the status quo of TM's pharmacological research, in hope of serving a reference value for the promotion of the modernization of TM and understanding of TM among the medical scholars.

Chronic oxytocin administration as a tool for investigation and treatment: A cross-disciplinary systematic review.

Oxytocin (OT) subserves various physiological, behavioral, and cognitive processes. This paired with the ability to administer OT with minimal and inconsistent side effects has spurred research to explore its therapeutic potential. Findings from single-dose studies indicate that OT administration may be beneficial, at least under certain circumstances. The state of the field, however, is less clear regarding effects from chronic OT administration, which more closely resembles long-term treatment. To address this gap, this review synthesizes existing findings on the use of chronic OT administration in animal and human work. In addition to detailing the effects of chronic OT administration across different functional domains, this review highlights factors that have contributed to mixed findings. Based on this review, a basic framework of interrelated regulatory functions sensitive to chronic OT administration is offered. The paper also identifies future research directions across different contexts, populations, and outcomes, specifically calling for more systematic and standardized research on chronic OT administration in humans to supplement and expand what is currently known from preclinical work.

State-of-the-art: functional fluorescent probes for bioimaging and pharmacological research.

Cardiovascular diseases, neuropsychiatric disorders, and cancers seriously endanger human health. Mechanistic and pharmacological mechanisms of candidate drugs are central to the translational paradigm. Since many signal transduction and molecular events are implicated in these diseases, a novel method to interrogate the key pharmacological mechanisms is required to accelerate innovative drug discovery. Much attention now focuses on the real-time visualization of molecular disease events to yield new insights to the pathogenesis of the diseases. This review focuses on recent advances in the development of chemical probes for imaging pathological events to facilitate the study of the underlying pharmacodynamics and toxicity involved. As reviewed here, optical imaging is now frequently viewed as an indispensable technique in the field of biological research. Promoting interdisciplinary collaboration among chemistry, biology and medicine, is necessary to further refine functional fluorescent probes for diagnostic and therapeutic applications.

Interpretation of Prescription and Syndrome of Yangjing Zhongyu Tang and Its Modern Research Progress / 中国实验方剂学杂志

Yangjing Zhongyu Tang, from FU Qing-zhu Nvke, is a famous classical formula of clinical value for treating blood deficiency syndrome of female infertility in the Qing dynasty. The prescription seems plain, but it is rigorous and effective with high research value. In this paper, the ancient books and modern documents of Yangjing Zhongyu Tang were analyzed from the aspects of traceability of Chinese materia medica in the formula, pharmacological research, clinical research, etc. It could be concluded that the pharmacological studies of this formula were mostly to investigate the mechanism and efficacy of its treatment for infertility, but there was a lack of comprehensive interpretation of the structure, function and principle of pharmacodynamic substance in this formula. In this paper, combined with the contents of supramolecular imprinting template and network pharmacology, the new direction of pharmacological research of Chinese medicine compound was put forward. Quality control of Yangjing Zhongyu Tang mostly based on small molecule compounds, so it was suggested to break the inherent thinking, and increase the detection of macromolecule compounds and supramolecular of Chinese materia medica. The druggability of this formula involved in the preliminary study of decoctions, plasters and granules. Considering the quality stability of Chinese materia medica in the formula and the scientificity of druggability of this formula, the compatibility principle of traditional Chinese medicine (TCM) and modern supramolecular chemistry theory could be combined to study the change law of druggability of TCM before and after compatibility, so as to provide new reference materials for the follow-up clinical application and development of Yangjing Zhongyu Tang.

Research Progress on Hemostatic Pharmacological Effects and Clinical Application of Mineral Chinese Medicine / 中国实验方剂学杂志

Mineral Chinese medicine is an indispensable part in traditional Chinese medicine, with a history of several thousand years in research and utilization of medicinal mineral resources. It is a summary of the medical experience accumulated in numerous trials,observations and practices during the survival process of people of all nationalities, showing distinctive characteristics. At present,the scope of mineral medicine treatment involves internal medicine,surgery,gynecology,pediatrics,facial features and so on. The mineral Chinese medicine has broad clinical application in many kinds of hemorrhagic diseases,with rich experience in medication and remarkable curative effects. However, there are few papers in modern research, mainly concentrated in the 1970s-1990s. In this paper, the pharmacology and clinical application of mineral Chinese medicine with hemostatic effects in the last 40 years were reviewed, aiming to provide references for its clinical rational use in bleeding diseases,further development and utilization of mineral Chinese medicine resources of traditional Chinese medicine,in-depth study of material basis and action mechanism,and further exploration of mineral Chinese medicine resources. According to the statistics of the major Chinese medicine works,27 kinds of mineral drugs have hemostatic effects. The researches on hemostatic pharmacology of mineral Chinese medicine mainly focus on the analysis of mineral medicine elements and the effect of related elements on hemostasis,as well as the pharmacological experimental study on hemostasis, but the research is not deep-going and comprehensive. The clinical application of mineral Chinese medicine for hemostasis mainly includes digestive tract hemorrhage,hemoptysis,epistaxis,gingival hemorrhage,cerebral hemorrhage,post-abortion hemorrhage,metrorrhagia,uterine bleeding,hematochezia and external hemostasis.

The progress of pharmacological and clinical researches on Xiangsha-Liujunzi decoction / 国际中医中药杂志

To observe the progess of pharmacological and clinical researches on Xiangsha-Liujunzi decoction by literature reviews recently. Pharmacological study found that the Xiangsha-Liujunzi decoction can protect the gastric mucosa, regulate gastrointestinal endocrine function, promote apoptosis of hyperplasia epithelial cell lying the gastric mucosa, and promote antidepressant effect. Thus, Xiangsha-Liujunzi decoction could be used for gastrointestinal diseases and tumor postoperative gastrointestinal dysfunction caused by radiation and chemotherapy.

Study on Antitussive, Expectorant and Antiasthmatic Effect of Aqueous Extracts and Chemical Split Fractions ofMori Cortex / 世界科学技术-中医药现代化

This study was aimed to investigate the antitussive, expectorant and antiasthmatic effects of aqueous extracts and the chemical split fractions ofMori Cortex. Cough mice models induced by ammonia water were used to observe the effect on arresting cough. The phenol red expectoration method in mice was used to observe the effect on expelling phlegm. Histamine and acetylcholine mixture induced asthma model was used to observe the effect on relieving asthma. Isolated trachea model was used to observe the effect on relieving spasm. Compared with the control group, the low, medium and high doses of aqueous extracts ofM. Cortex can obviously decrease the frequency of cough, increase phenol red output of trachea in mice, prolong the latent period of asthma in guinea pigs, and increase the antispasmodic rate. The medium dose had the best effect. The comparison between different chemical split fractions ofM. Cortex and the control group showed that the 30% and 50% ethanol fraction ofM. Cortex can obviously decrease the frequency of cough and prolong the latent period of cough induced by ammonia water in mice, increase phenol red output of trachea in mice (P<0.05 orP<0.01); and 30% ethanol fraction and fatty oil fraction can prolong the latent period of asthma in guinea pigs (P< 0.05 orP<0.01). In addition, 30% ethanol fraction can obviously reduce the degree of tracheal contraction. It had certain effect of relieving spasm. It was concluded that aqueous extracts ofM. Cortex had better effects on relieving cough, expectorant and antiasthma. The effective part was the 30% ethanol fraction, which was the dose equivalent of 1/3 of the medium dose. It had significant effect on relieving cough, expectorant and antiasthma. The effect was equivalent to the medium dose of aqueous extracts of M. Cortex.

Research Ideas on Post-marketing Revaluation of Tibetan Medicine with Seventy-flavor Pearl Pill / 世界科学技术-中医药现代化

This study was aimed to carry the post-marketing revaluation on classical Tibetan medicine of the Seven-ty-flavor Pearl Pill, which will help improve its scientificity, safety and standardization in order to promote its indus- trial development. Literature mining method was used to summarize research information of the Seventy-flavor Pearl Pill, such as the clinical pharmacy sorting. Meanwhile, the successful example of Padma-28 was referred in the analysis of deficiencies in the indications of Seventy-flavor Pearl Pill. The results showed the present situation of clinical combination therapy, pharmacology and toxicology study of Seventy-flavor Pearl Pill. It was concluded that the building of new model of post-marketing revaluation on the Seventy-flavor Pearl Pill can provide re-evaluation scientific basis for Tibetan medicine on its clinical effectiveness and safety.