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The PI3K/AKT/GSK-3β signaling pathway plays a pivotal role in numerous physiological and pathological processes, including cell proliferation, apoptosis, differentiation, and metabolic regulation. Aberrant activation of the PI3K/AKT pathway is intricately linked to development of tumor. GSK-3β, belonging to the serine/threonine protein kinase family, is crucial in the pathogenesis of liver cancer. As a key rate-limiting enzyme in the glucose metabolism pathway, GSK-3β significantly impacts the growth, proliferation, metastasis, and apoptosis of liver cancer cells. It is also implicated in chemotherapy resistance. Elevated expression of GSK-3β diminishes the sensitivity of liver cancer cells to chemotherapeutic agents, thereby playing a substantial role in the development of drug resistance. Consequently, targeting of GSK-3β, particularly within the PI3K/AKT signaling pathway, is regarded as a promising therapeutic strategy for liver cancer. The precise identification and subsequent modulation of this pathway represent a substantial potential for innovative clinical interventions in the management of liver cancer.

Diabetic cardiomyopathy (DCM) is a specific heart condition in diabetic patients, which is a major cause of heart failure and significantly affects quality of life. DCM is manifested as abnormal cardiac structure and function in the absence of ischaemic or hypertensive heart disease in individuals with diabetes. Although the development of DCM involves multiple pathological mechanisms, mitochondrial dysfunction is considered to play a crucial role. The regulatory mechanisms of mitochondrial dysfunction mainly include mitochondrial dynamics, oxidative stress, calcium handling, uncoupling, biogenesis, mitophagy, and insulin signaling. Targeting mitochondrial function in the treatment of DCM has attracted increasing attention. Studies have shown that plant secondary metabolites contribute to improving mitochondrial function and alleviating the development of DCM. This review outlines the role of mitochondrial dysfunction in the pathogenesis of DCM and discusses the regulatory mechanism for mitochondrial dysfunction. In addition, it also summarizes treatment strategies based on plant secondary metabolites. These strategies targeting the treatment of mitochondrial dysfunction may help prevent and treat DCM.

The skin barrier is essential for maintaining the body’s internal homeostasis, protecting against harmful external substances, and regulating water and electrolyte balance. Traditional Chinese Medicine (TCM) offers notable advantages in restoring skin barrier function due to its diverse components, targets, and pathways. Recent studies have demonstrated that active ingredients in TCM can safely and effectively repair damaged skin barriers, reinstating their proper functions. This review article provides a comprehensive overview of the mechanisms underlying skin barrier damage and explores how the bioactive constituents of TCM contribute to skin barrier repair, thereby offering a theoretical framework to inform clinical practices.

Abstract Tumours do not exist in isolation from the organism; their growth, proliferation, motility, and immunosuppressive response are intricately connected to the tumour’s microenvironment. As tumour cells and the microenvironment coevolve, an inflammatory microenvironment ensues, propelling the phenomenon of inflammation-cancer transformation—an idea proposed by modern medicine. This review aims to encapsulate the array of representative factors within the tumour’s inflammatory microenvironment, such as interleukins (IL-6, IL-10, IL-17, IL-1β), transforming growth factor-beta (TGF-β), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Moreover, drawing upon research in traditional Chinese medicine (TCM) and pharmacology, we explore the delicate interplay between these factors and tumour-associated inflammatory cells: tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (TANs) and dendritic cells (DCs). By analyzing the tumour-promoting effects of these entities, we delve into the connotations of Academician Tong Xiao-lin’s novel model of “state-target differentiation” and its application in the diagnosis and treatment of tumours. Our aim is to enhance the precision and targeting of tumour treatment in clinical practice. Delving deeper into our understanding of tumour pathogenesis through the lens of modern medicine, we discern the key etiology and pathogenesis throughout the entire developmental stage of tumours, unveiling the evolutionary patterns of Chinese Medicine (CM) states: heat state → phlegm state → stagnation state → deficiency state. Building upon this foundation, we devised a state-regulating formula. Simultaneously, drawing on pharmacological research in traditional Chinese medicine (TCM), we meticulously identified a range of targeted drugs that effectively modulate the aforementioned tumour-related mediators. This comprehensive strategy—a harmonious integration of state identification, target recognition, and simultaneous regulation—aims to elevate clinical efficacy. The fusion of TCM with Western medicine in tumour treatment introduces novel dimensions to the precise and refined application of TCM in clinical practice.

Context Gnetum montanum Markgr. (Gnetaceae) is used to treat rheumatic arthralgia and bruises in the clinic.Objective To exam the activity and mechanism of G. montanum extract (GME) against colon cancer cells SW480.Materials and methods The anti-proliferative activity of GME (0–120 μg/mL) on SW480 cells was determined using MTS assay at 24, 48, and 72 h. The in vitro activity of GME (0–120 μg/mL) on SW480 cells was investigated using flow cytometry and western blotting analysis. The in vivo activity of GME was evaluated using xenograft tumour model of zebrafish and nude mice. The chemical composition of GME was detected by using HPLC–MS/MS.Results The IC50 value SW480 cells viability by GME were 126.50, 78.25, and 50.77 μg/mL, respectively, for 24, 48, and 72 h. The experiments showed that apoptotic cells and G2/M phase cells increased from 20.81 to 61.53% (p

As a neurodegenerative disease, Alzheimer’s disease (AD) is characterized by synaptic loss, extracellular plaques of amyloid accumulation, hyperphosphorylation of tau, and neuroinflammation. Various biological processes are affected by epitranscriptomic modifications, which regulate the metabolism of mRNA in cells and regulate the expression of genes. In response to changes in m6A modification levels, the nervous system becomes dysfunctional and plays a significant role in the development of Alzheimer’s disease. As a result of recent research, this paper reviews advances in the understanding of the regulatory mechanisms of m6A modification in the occurrence and development of AD. In addition, the article discusses recent research techniques related to animal models of m6A and AD. Furthermore, it discusses the possibility of studying the pathogenesis of AD at the level of the epitranscriptome, identifying early diagnostic markers, and screening for effective treatment options.

Aquaporins (AQPs) are a family of transmembrane proteins expressed in various organ systems. Many studies have shown that the abnormal expression of AQPs is associated with gastrointestinal, skin, liver, kidneys, edema, cancer, and other diseases. The majority of AQPs are expressed in the digestive system and have important implications for the physiopathology of the gastrointestinal tract as well as other tissues and organs. AQP regulators can prevent and treat most gastrointestinal-related diseases, such as colorectal cancer, gastric ulcer, and gastric cancer. Although recent studies have proposed clinically relevant AQP-targeted therapies, such as the development of AQP inhibitors, clinical trials are still lacking and there are many difficulties. Traditional Chinese medicine (TCM) has been used in China for thousands of years to prevent, treat and diagnose diseases, and is under the guidance of Chinese medicine (CM) theory. Herein, we review the latest research on the regulation of AQPs by TCMs and their active components, including Rhei Radix et Rhizoma, Atractylodis macrocephalae Rhizoma, Salviae miltiorrhizae Radix et Rhizoma, Poria, Astragali radix, and another 26 TCMs, as well as active components, which include the active components include anthraquinones, saponins, polysaccharides, and flavonoid glycosides. Through our review and discussion of numerous studies, we attempt to explore the regulatory effects of TCMs and their active components on AQP expression in the corresponding parts of the body in terms of the Triple Energizer concept in Chinese medicine defined as “upper energizer, middle energizer, and lower energizer,”so as to offer unique opportunities for the development of AQP-related therapeutic drugs for digestive system diseases.

In recent years, activation of thermal transient receptor potential (TRP) ion channels at a range of temperatures has received widespread attention as a target for traditional Chinese medicine (TCM) to regulate body temperature and relieve pain. Discovery of transient receptor potential vanilloid 1 (TRPV1) was awarded a Nobel Prize, reflecting the importance of these channels. Here, the regulatory effects of TCMs and their active ingredients on TRP ion channels are reviewed, and future directions for research on the cold, hot, warm, cool, and neutral natures of TCMs are considered. In herbs with cold, hot, warm, cool, and neutral natures, we found 29 TCMs with regulatory effects on TRP ion channels, including Cinnamomi Cortex, Capsici Fructus, Rhei Radix et Rhizoma, Macleayae cordatae Herba, Menthae Haplocalycis Herba, and Rhodiolae Crenulatae Radix et Rhizoma. Although some progress has been made in understanding the regulation of TRP ion channels by TCMs and their ingredients, the molecular mechanism by which TCMs have this effect remains to be further studied. We hope this review will provide a reference for further research on the cold, hot, warm, cool, and neutral natures of TCMs.

Tetrandrine (Tet), derived from the traditional Chinese herb Fangji, is a class of natural alkaloids with the structure of bisbenzylisoquinoline, which has a wide range of physiological activities and significant pharmacfological effects. However, studies and clinical applications have revealed a series of drawbacks such as its poor water solubility, low bioavailability, and the fact that it can be toxic to humans. The results of many researchers have confirmed that chemical structural modifications and nanocarrier delivery can address the limited application of Tet and improve its efficacy. In this paper, we summarize the anti-tumor efficacy and mechanism of action, anti-inflammatory efficacy and mechanism of action, and clinical applications of Tet, and describe the progress of Tet based on chemical structure modification and nanocarrier delivery, aiming to explore more diverse structures to improve the pharmacological activity of Tet and provide ideas to meet clinical needs.

Context Although the roots and stems of Kadsura coccinea (Lem.) A. C. Smith. [Schisandraceae] are herbs and traditional foods in Li nationality, its toxicity remains unclear. Objective To study developmental toxicity of K. coccinea consumption and explain underlying mechanisms. Materials and methods Zebrafish were applied to assess LC50 values of hydroethanol extract (KCH) and water extract (KCW) of Kadsura coccinea. In further study, three concentrations groups of KCH (3.75, 7.5 and 15 μg/mL for embryo, 7.5, 15 and 30 μg/mL for larvae) and control group (n = 30) were administered. At specific stages of zebrafish development, spontaneous movement, hatching rate, etc., were measured. Gene expressions related to developmental toxicity were examined. Results The LC50 value of KCH (24 or 45 μg/mL) was lower than KCW (1447 or 2011 μg/mL) in embryos or larvae. The inhibited spontaneous movement (20%), hatching rate (20%), body length (12%) and eye area (30%) were observed after KCH treatment. Moreover, the decreased liver areas (25%) and fluorescence intensity (33%), increased ALT (37%) and AST levels (42%) were found in larvae treated with KCH (30 μg/mL). The increased ROS (89%), MDA concentrations (30%), apoptosis generation (62%) and decreased T-SOD activity (16%) were also observed. The represented genes of developmental hepatotoxicity, oxidative stress and apoptosis in zebrafish were activated after KCH (15 or 30 μg/mL) treatment. Discussion and conclusions These results demonstrate that KCH has developmental toxicity on zebrafish. Our study provides a scientific basis for further research on the toxicity of Kadsura coccinea.

Colon cancer is the third most common cancer in the world with a high mortality rate. At present, surgery combined with radiotherapy and chemotherapy is the primary treatment, but patient prognosis remains poor. Traditional Chinese medicine (TCM) has become a complementary and alternative source of anti-cancer drugs. Camellia nitidissima Chi (CNC) is a TCM used to treat a variety of cancers. However, the role of CNC in cancer remains elusive, and its effect and mechanism on colon cancer have not been reported. Here, we show that CNC exerts an excellent inhibitory effect on colon cancer proliferation and apoptosis induction in vitro and in vivo. We performed label free-based quantitative proteomic analysis to evaluate the HCT116 cells treated with CNC. Our data revealed a total of 363 differentially expressed proteins, of which 157 were up-regulated and 206 down-regulated. Gene Ontology enrichment analysis showed that these proteins were involved in tumor occurrence and development through multiple biological processes such as cell proliferation, cell apoptosis, cell cycle, and cell death. Interestingly, we also found significant changes in ferroptosis pathways. The role of essential proteins glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HMOX1) were verified. CNC decreased the expression of GPX4 and increased the expression of HMOX1 at the mRNA and protein levels in vivo and in vitro. Collectively, these findings reveal that CNC regulates colon cancer progression via the ferroptosis pathway and could be an attractive treatment for colon cancer.

Yizhi Granule (YZG) is a health food containing six traditional Chinese medicines (TCMs). It improves memory barriers in rat experiments. Here, we describe the first fast and sensitive ultraperformance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-Q-TOF MS) method for analyzing YZG in plasma. We used this technique for studies in cynomolgus monkey plasma. By comparing retention time, MS, and MS/MS data of reference compounds, 70 compounds were detected in YZG. Of these, 63 were identified including 60 saponins, 2 flavones, and 1 methyl ester. There were 33 saponins, 1 flavone, and 1 methyl ester in the plasma. Next, to study the therapeutic properties of YZG, the neuroprotective effect of some of the absorbed components was evaluated using PC12 cell damage caused by the Aβ25–35 model. The results showed that 9 compounds protect PC12 cells from Aβ25–35 with cell viability (%) of 111.00 ± 8.12 (G-Rb1), 102.20 ± 4.22 (G-Rb2), 100.34 ± 6.47 (G-Rd), 102.83 ± 2.10 (G-Re), 101.68 ± 7.64 (NG-Fa), 101.19 ± 7.83 (NG-R1), 102.53 ± 0.55 (NG-R2), 106.88 ± 4.95 (gypenoside A), and 103.95 ± 4.11 (gypenoside XLIX), respectively, versus the control group (87.51 ± 6.59). These results can reveal the real pharmacodynamic basis of YZG and provide a theoretical basis for subsequent studies. It can also provide some references for the research of Alzheimer’s disease.

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Mangiferin (2-ß-D-glucopyranosyl-1,3,6,7-tetrahydroxy-9H-xanthen-9-one), a xanthanoid, is one of the major compounds isolated from mango leaves and bark fruit. Previous studies have identified several properties of mangiferin, such as preventing microbial growth, reducing oxidative stress and helping reduce risk of diabetes. The aim of the present study is to explore the potential anti-dementia effects of Mangiferin in a senescence-accelerated mouse prone 8 (SAMP8) mouse model. Morris water maze (MWM) test showed that mangiferin significantly improved the learning and memory retention in SAMP8 mice. In addition, mangiferin reduced the damage in hippocampal neurons and mitochondria, and decreased the expression of amyloid-ß (Aß1-40 and Aß1-42); however, no influence on the expression of amyloid precursor protein (APP) within the brain of SAMP8 mice. Moreover, Mangiferin inhibited lipid peroxidation (LPO). In conclusion, we provided evidences to show that mangiferin significantly restored the learning and memory impairment in the SAMP8 mouse model, and reduced the pathological injury in hippocampal by modulating lipid oxidation and amyloid-ß deposition in the brain. [ABSTRACT FROM AUTHOR]

[Objectives] To study the effects of Mangiferin (MGF) on TNF-α, iNOS, ICAM-1 and its mRNA expression in the heart, brain and kidneys of spontaneously hypertensive rats (SHR), and reveal the mechanism of its anti-inflammatory injury in hypertension target organs. [Methods] SHRs were randomly divided into 5 groups: the model group, the high-dose, medium-dose, low-dose MGF groups and the Benazepril group, with 8 rats in each group, WKY rats were used for the normal control group. Besides, on-invasive blood pressure (BP) instruments were used to measure systolic blood pressure in the rats' tail artery, western blot was used to analyze the expression of TNF-α, iNOS, ICAM-1 and reverse transcription-polymerase chain reaction (RT-PCR) was used to anayze the expression of TNF-α, iNOS, ICAM-1 mRNA. [Results] Compared with the normal control group, the model group's BP level was significantly increased (P<0.01), but the MGF had no significant lowering BP effect (P>0.05); compared with the norma control group, the expression of TNF-α, iNOS, ICAM-1 and its' mRNA in the model group was significantly increased (P<0.05 or P<0.01), and MGF could reduce the level of expression of these inflammatory cytokines (P<0.05 or P<0.01); between the Benazepril group and high-dose, medium-dose, low-dose MGF groups, most of the indicators had no significant diference (P>0.05). [Conclusions] MGF had no significant lowering BP effect, SHR showed innflammatory injury in the heat, brain and kidneys, MGF showed improvement on the inflammatory injury, and the ati-inflammation mechaism may be associated with lowering TNF-α, iNOS and ICAM-1 and its mRNA expression. [ABSTRACT FROM AUTHOR]