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Ganoderma lucidum (G. lucidum) is a traditional edible and medicinal mushroom in China. The main bioactive components in G. lucidum include triterpenoids, polysaccharides, steroids, and sterols. Ganoderic acids (GAs) are one of the most abundant triterpenoids found in G. lucidum, garnering significant attention from researchers in the fields of medicine and health care. We summarize the extensive studies on the physiological function of GAs in anti-cancer, anti-inflammatory, radiation protection, anti-aging, liver protection, anti-microbial, and neuroprotection areas, among others. This review provides a comprehensive overview of the recent advances in the bioactivities and pharmacological mechanisms of GAs, aiming to delineate the current research directions and the state of the art in this field. This analysis helps to rapidly identify new bioactivities of GAs and understand their mechanisms, leading to more effective treatments for various diseases. [ABSTRACT FROM AUTHOR]

Functional gastrointestinal disorders (FGIDs) and inflammatory bowel disease (IBD) are common clinical disorders characterized by recurrent diarrhea and abdominal pain. Although their pathogenesis has not been fully clarified, disruptions in intestinal motility and immune function are widely accepted as contributing factors to both conditions, and the brain-gut axis plays a key role in these processes. Traditional Chinese Medicine (TCM) employs a holistic approach to treatment, considers spleen and stomach impairments and liver abnormality the main pathogenesis of these two diseases, and offers a unique therapeutic strategy that targets these interconnected pathways. Clinical evidence shows the great potential of TCM in treating FGIDs and IBD. This study presents a systematic description of the pathological mechanisms of FGIDs and IBD in the context of the brain-gut axis, discusses clinical and preclinical studies on TCM and acupuncture for the treatment of these diseases, and summarizes TCM targets and pathways for the treatment of FGIDs and IBD, integrating ancient wisdom with contemporary biomedical insights. The alleviating effects of TCM on FGID and IBD symptoms are mainly mediated through the modulation of intestinal immunity and inflammation, sensory transmission, neuroendocrine-immune network, and microbiota and their metabolism through brain-gut axis mechanisms. TCM may be a promising treatment option in controlling FGIDs and IBD; however, further high-quality research is required. This review provides a reference for an in-depth exploration of the interventional effects and mechanisms of TCM in FGIDs and IBD, underscoring TCM's potential to recalibrate the dysregulated brain-gut axis in FGIDs and IBD. [ABSTRACT FROM AUTHOR]

Due to their complex pathological mechanisms, neurodegenerative diseases have brought great challenges to drug development and clinical treatment. Studies have shown that many traditional Chinese medicines have neuroprotective pharmacological activities such as anti-inflammatory and anti-oxidation properties and have certain effects on improving the symptoms of neurodegenerative diseases and delaying disease progression. Flavonoids are the main active components of many traditional Chinese medicines for the treatment of neurodegenerative diseases. These compounds have a wide range of biological activities, including anti-inflammatory, anti-oxidative stress, regulation of autophagy balance, inhibition of apoptosis, and promotion of neuronal regeneration. This paper focuses on the neuroprotective effects of six common flavonoids: quercetin, rutin, luteolin, kaempferol, baicalein, and puerarin. It then systematically reviews their characteristics, mechanisms, and key signaling pathways, summarizes the common characteristics and laws of their neuroprotective effects, and discusses the significance of strengthening the research on the neuroprotective effects of these compounds, aiming to provide reference for more research and drug development of these substances as neuroprotective drugs. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM). Radix Astragali (RA), a frequently used Chinese herbal medicine in the Leguminosae family, Astragalus genus, with its extracts, has been proven to be effective in DN treatment both in clinical practice and experimental studies. RA and its extracts can reduce proteinuria and improve renal function. They can improve histopathology changes including thickening of the glomerular basement membrane, mesangial cell proliferation, and injury of endothelial cells, podocytes, and renal tubule cells. The mechanisms mainly benefited from antioxidative stress which involves Nrf2/ARE signaling and the PPARγ‐Klotho‐FoxO1 axis; antiendoplasmic reticulum stress which involves PERK‐ATF4‐CHOP, PERK/eIF2α, and IRE1/XBP1 pathways; regulating autophagy which involves SIRT1/NF‐κB signaling and AMPK signaling; anti‐inflammation which involves IL33/ST2 and NF‐κB signaling; and antifibrosis which involves TGF‐β1/Smads, MAPK (ERK), p38/MAPK, JNK/MAPK, Wnt/β‐catenin, and PI3K/AKT/mTOR signaling pathways. This review focuses on the clinical efficacy and the pharmacological mechanism of RA and its representative extracts on DN, and we further document the traditional uses of RA and probe into the TCM theoretical basis for its application in DN. [ABSTRACT FROM AUTHOR]

Polysaccharides are one of the most important components of traditional Chinese medicine (TCM) and have been extensively studied for their immunomodulatory properties. The functions and effects of TCM polysaccharides are closely related to the gut microbiota, making the study of their interaction a hot topic in the field of TCM metabolism. This review follows two main inquiries: first, how the gut microbiota breaks down TCM polysaccharides to produce bioactive metabolites; and second, how TCM polysaccharides reshape the gut microbiota as a carbon source. Understanding the interaction mechanism involves a challenging equation of the structural association of TCM polysaccharides with the metabolic activities of the microbiota. This review has meticulously searched, partially organized literature spanning the past decade, that delves into the interaction mechanism between TCM polysaccharides and gut microbiota. It also gives an overview of the complex factors of the elusive "polysaccharides‐bond‐bacteria‐enzyme" equation: the complexity of polysaccharide structures, the diversity of glycosidic bond types, the communal nature of metabolizing microbiota, the enzymes involved in functional degradation by microbiota, and the hierarchical roles of polysaccharide utilization locus and gram‐positive PULs. Finally, this review aims to facilitate discussion among peers in the field of TCM microbiota and offers prospects for research in related fields, paving the way for pharmacological studies on TCM polysaccharides and gut microbiota therapeutics, and providing a reference point for further clinical research. [ABSTRACT FROM AUTHOR]

Cosmos caudatus is a widely used traditional medicinal plant in Indonesia for cancer treatment. However, the mechanism of action of plants in treating breast neoplasms remains unclear. Thus, the active ingredients of C. caudatus and possible molecular pathways against breast neoplasms were investigated using pharmacological networks. The active compounds were screened using Lipinski and ADME parameters. Targets for the compounds were obtained using SwissTargetPrediction. Target diseases were identified using the Therapeutic Target Database, whereas disease pathways were analyzed using the Kyoto Encyclopedia of Genes and Genomes. Network pharmacology was constructed using Cytoscape. Protein-protein interactions were constructed using STRING. Gene ontology and KEGG were analyzed using DAVID. Molecular docking confirmed that the compounds and targets exhibited the best interactions. The compounds, targets, and pathways with the highest degrees in the breast neoplasm network were eriodictyol, ABCC1, and signal transduction, respectively. EGFR is the key target of PPIs. GO enrichment in BP, MF, CC, and KEGG regulated NF-KB transcription factor activity, chromatin, transcription coactivator binding, and pathways in cancer, respectively. Molecular docking with the best score on interaction 5-O-methylvisammioside-SLC2A1 (PDB ID: 6THA) (-10.3 kcal mol-1). The compound 5-O-methylvisammioside may have pharmacological activity in breast cancer through signal transduction pathways. [ABSTRACT FROM AUTHOR]

Abstract Background Acute gouty arthritis (AGA) is classified as ‘arthritis’ in traditional Chinese medicine (TCM) theory. Shirebi granules (SGs), derived from the classic prescription SiMiaoWan, exerts satisfying therapeutic efficacy in ameliorating AGA clinically. However, the underlying mechanisms of SGs against AGA remain unclarified. Methods AGA-related biological processes, signal pathways and biomarker genes were mined from the GEO database through bioinformatics. SGs components were systematically recognized using the UPLC-Q-TOF–MS/MS. A correlation network was established based on the biomarker genes and the chemical components, from which the signal pathway used for further study was selected. Finally, we established an AGA model using SD rats injected with monosodium urate (MSU) in the ankle joint for experimental validation. A combination of behavioral tests, H&E, safranin O- fast green, western blotting, and immunofluorescence were employed to reveal the mechanism of action of SGs on AGA. Results The deterioration of AGA was significantly related to the imbalance between immunity and inflammation, neutrophil chemotaxis and inflammatory factor activation. HDAC5, PRKCB, NFκB1, MPO, PRKCA, PIK3CA were identified to be the candidate targets of SGs against AGA, associated with neutrophil extracellular traps (NETs) signal pathway. Animal experiments demonstrated that SGs effectively repaired cartilage damage, blocked TLR4 activation, and inhibited the expression of NETs indicators and inflammatory factors. In addition, SGs prominently alleviated joint redness and swelling, improved joint dysfunction, inhibited inflammatory infiltration of AGA rats. Conclusion Our data reveal that SGs may effectively alleviate the disease severity of AGA by suppressing NETs-promoted imbalance between immunity and inflammation.

Fibrosis is a public health issue of great concern characterized by the excessive deposition of extracellular matrix, leading to the destruction of parenchymal tissue and organ dysfunction that places a heavy burden on the global healthcare system due to its high incidence, disability, and mortality. Salvianolic acid B (SalB) has positively affected various human diseases, including fibrosis. In this review, we concentrate on the anti-fibrotic effects of SalB from a molecular perspective while providing information on the safety, adverse effects, and drug interactions of SalB. Additionally, we discuss the innovative SalB formulations, which give some references for further investigation and therapeutic use of SalB's antifibrotic qualities. Even with the encouraging preclinical data, additional research is required before relevant clinical trials can be conducted. Therefore, we conclude with recommendations for future studies. It is hoped that this review will provide comprehensive new perspectives on future research and product development related to SalB treatment of fibrosis and promote the efficient development of this field. [ABSTRACT FROM AUTHOR]

Background: Acute gouty arthritis (AGA) is classified as 'arthritis' in traditional Chinese medicine (TCM) theory. Shirebi granules (SGs), derived from the classic prescription SiMiaoWan, exerts satisfying therapeutic efficacy in ameliorating AGA clinically. However, the underlying mechanisms of SGs against AGA remain unclarified. Methods: AGA-related biological processes, signal pathways and biomarker genes were mined from the GEO database through bioinformatics. SGs components were systematically recognized using the UPLC-Q-TOF–MS/MS. A correlation network was established based on the biomarker genes and the chemical components, from which the signal pathway used for further study was selected. Finally, we established an AGA model using SD rats injected with monosodium urate (MSU) in the ankle joint for experimental validation. A combination of behavioral tests, H&E, safranin O- fast green, western blotting, and immunofluorescence were employed to reveal the mechanism of action of SGs on AGA. Results: The deterioration of AGA was significantly related to the imbalance between immunity and inflammation, neutrophil chemotaxis and inflammatory factor activation. HDAC5, PRKCB, NFκB1, MPO, PRKCA, PIK3CA were identified to be the candidate targets of SGs against AGA, associated with neutrophil extracellular traps (NETs) signal pathway. Animal experiments demonstrated that SGs effectively repaired cartilage damage, blocked TLR4 activation, and inhibited the expression of NETs indicators and inflammatory factors. In addition, SGs prominently alleviated joint redness and swelling, improved joint dysfunction, inhibited inflammatory infiltration of AGA rats. Conclusion: Our data reveal that SGs may effectively alleviate the disease severity of AGA by suppressing NETs-promoted imbalance between immunity and inflammation. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is one of the common malignant tumors of digestive tract, which seriously threatens the life of patients due to its high incidence rate, strong invasion, metastasis, and prognosis. At present, the main methods for preventing and treating HCC include medication, surgery, and intervention, but patients frequently encounter with specific adverse reactions or side effects. Many Traditional Chinese medicine can improve liver function, reduce liver cancer recurrence and have unique advantages in the treatment of HCC because of their acting mode of multi-target, multi-pathway, multicomponent, and multi-level. Sesquiterpenoids, a class of natural products which are widely present in nature and exhibit good anti-tumor activity, and many of them possess good potential for the treatment of HCC. This article reviewed the anti-tumor activities, natural resources, pharmacological mechanism of natural sesquiterpenoids against HCC, providing the theoretical basis for the prevention and treatment of HCC and a comprehensive understanding of their potential for development of new clinical drugs. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a chronic condition that can be managed with treatment, but it is challenging to get IBD cured. Resveratrol, a non-flavonoid polyphenolic organic compound derived from various plants, has a potential effect on IBD. The current research was set out to investigate the therapeutic effects of resveratrol on animal models of IBD. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Chinese databases was performed. The literature search process was completed independently by two people and reviewed by a third person. The risk of bias in the included literature was assessed using the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Stroke (CAMARADES) 10-point quality checklist. The meta-analysis utilized Review Manager 5.4 software to evaluate the efficacy of resveratrol, with histopathological index as the primary outcome measure. Subgroup analysis was conducted based on this indicator. Additionally, meta-analyses were carried out on different outcomes reported in the literature, including final disease activity index, final body weight change, colon length, splenic index, and inflammatory factors. Results: After conducting a thorough literature search and selection process, a total of 28 studies were ultimately included in the analysis. It was found that over half of the selected studies had more than five items with low risk of bias in the bias risk assessment. Relevant datas from included literature indicated that the histopathological index of the resveratrol group was significantly lower than that of the control group (WMD = -2.58 [-3.29, -1.87]). Subgroup analysis revealed that higher doses of resveratrol (>80 mg/kg) had a better efficacy (WMD = -3.47 [- 4.97, -1.98]). Furthermore, The data summary and quantitative analysis results of SI and colon length also showed that resveratrol was effective in alleviating intestinal mucosal pathological injury of IBD. In terms of biochemical indicators, the summary analysis revealed that resveratrol affected interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-a (TNF-a), transforming growth factor-ß (TGF-ß), interferon-γ (IFN-γ), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) significantly. These effects may be attributed to the mechanism of resveratrol in regulating immune response and inhibiting oxidative stress. Conclusion: This review suggests that resveratrol demonstrated a notable therapeutic impact in preclinical models of IBD, particularly at doses exceeding 80 mg/kg. This efficacy is attributed to the protective mechanisms targeting the intestinal mucosa involved in the pathogenesis of IBD through various pathways. As a result, resveratrol holds promising prospects for potential clinical use in the future. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of Herba Houttuyniae on the biological behavior of liver cancer cells and related potential molecular mechanisms. Methods Liver cancer cells SMMC-7721 and SK-Hep-1 were treated with different concentrations of Herba Houttuyniae extract. Cell viability was detected by CCK-8. Transwell assays were used to evaluate the migration and invasion ability of the liver cancer cells. The expression of the metastatic-related protein MMP-9 was detected by cellular immunofluorescence assay. The reactive oxygen species(ROS) levels in the cells were measured by using ROS detection kit, and cell apoptosis was assessed by TUNEL staining. The expression levels of apoptosis-related proteins were analyzed by Western blot. Network pharmacology was employed to screen the active components of Herba Houttuyniae and to construct a protein-protein interaction (PPI) network to identify the therapeutic targets of Herba Houttuyniae in liver cancer. GO and KEGG pathway enrichment analyses were performed to explore the signaling pathways associated with the target of Herba Houttuyniae in anti-liver cancer. The qRT-PCR was used to detect the mRNA expression levels of key targets. Results The CCK-8, Transwell, and cellular immunofluorescence assays indicated that Herba Houttuyniae extracts inhibited the viability, migration, and invasion abilities of SMMC-7721 and SK-Hep-1 cells, as well as the expression of the metastasis- related protein MMP -9 (all P<0.05). TUNEL staining, ROS detection, and Western blot results showed that Herba Houttuyniae extracts promoted apoptosis in SMMC-7721 and SK-Hep-1 cells, elevated intracellular ROS levels, and increased the expression of the pro-apoptotic protein BAX (all P<0.05). Network pharmacology predicted that Herba Houttuyniae treated liver cancer primarily by targeting TNF, AKT1, TP53, etc. involving cancer, TNF, PI3K-AKT and other signaling pathways. The qRT-PCR confirmed that Herba Houttuyniae extracts decreased the mRNA expression levels of TNF -α and AKT1 genes, while increased the mRNA expression level of the TP53 gene in SMMC-7721 and SK-Hep-1 cells (all P<0.05). Conclusions Herba Houttuyniae may inhibit the viability, migration, and invasion abilities of liver cancer cells and promote the apoptosis by regulating genes such as TNF, AKT1, and TP53. [ABSTRACT FROM AUTHOR]

BackgroundIn recent years, the incidence of depression, recognized as a serious psychological disorder, has escalated rapidly. Rehmannia glutinosa DC. (Scrophulariaceae; Rehmanniae Radix, Crude drug) and Lilium lancifolium Thunb. (Liliaceae; Lilii bulbus, Crude drug) constitute a classic anti-depressant combination, exhibiting pharmacological effects that include anti-depressive, anti-anxiety, and anti-inflammatory properties. Current clinical studies have demonstrated that Baihe Dihuang Decoction, a traditional Chinese herbal compound, is effective in treating depression. However, the majority of scholars have predominantly examined Rehmannia glutinosa and Lilium in isolation, and a comprehensive elucidation of their principal active metabolites and pharmacological mechanisms remains lacking.MethodsA comprehensive literature search was conducted as of 29 September 2024, utilizing databases such as PubMed, CNKI, Wanfang Data, Baidu Scholar, and Google Scholar. Additionally, classical texts on Chinese herbal medicine, the Chinese Pharmacopoeia, as well as doctoral and master’s theses, were included in the collected materials. The search employed specific terms including “R. glutinosa,” “Lilium,” “Baihe Dihuang decoction,” “application of Baihe Dihuang decoction,” “pathogenesis of depression,” and “pharmacological action and mechanism of depression.ResultsThis paper reviewed the traditional applications and dosages of the R. glutinosa-Lilium as documented in Chinese medical classics, thereby establishing a foundation for the contemporary development and clinical application of the classical formula Baihe Dihuang Decoction. Additionally, recent years have seen a comprehensive review of the pharmacological effects and mechanisms of R. glutinosa-Lilium and its principal metabolites in the context of depression.ConclusionThis paper has reviewed the active metabolites of R. glutinosa-Lilium and demonstrated its efficacy in the treatment of depression, as well as its role in modulating the underlying mechanisms of the disorder. The findings aim to serve as a reference for further research into the mechanisms of depression, its clinical applications, and the development of novel therapeutic agents.

Dendrobium is a precious Chinese herbal medicine, which belongs to the genus Orchidaceae. Ancient records and modern pharmacological research show that Dendrobium has pharmacological effects such as anti-tumor, antioxidant regulating immunity and blood glucose, and anti-aging. Dendrobium contains polysaccharides, alkaloids, bibenzyl, sesquiterpenes, phenanthrene, polyphenols and other types of chemicals. Its pharmacological activity is closely related to these chemical components. For example, dendrobium extracts can achieve anti-tumor effects by inhibiting tumor cell proliferation and metastasis, promoting cell apoptosis and ferroptosis, or increasing cell sensitivity to chemotherapy drugs. It enhances immunity by regulating immune cell activity or cytokine release. In addition, it can alleviate neurodegenerative diseases by protecting nerve cells from apoptotic damage. In recent years, research reports on biologically active compounds in Dendrobium have shown a blowout growth, which makes us realize that it is meaningful to continuously update the research progress on the components and pharmacological regulatory mechanism of this traditional Chinese medicine. By classifying the collected chemical components according to different chemical structures and summarizing their pharmacological mechanisms, we investigated the current research progress of Dendrobium and provide a more comprehensive scientific foundation for the further development and clinical transformation of Dendrobium in the future.

This study aimed to explore the mechanisms through which salvianolic acid B (Sal-B) exerts its effects during myocardial ischemia-reperfusion injury (MI/RI), aiming to demonstrate the potential pharmacological characteristics of Sal-B in the management of coronary heart disease. First, Sal-B-related targets and MI/RI-related genes were compiled from public databases. Subsequent functional enrichment analyses using the protein–protein interaction (PPI) network, gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) predicted the core targets and approaches by which Sal-B counters MI/RI. Second, a Sal-B-treated MI/RI mouse model and oxygen–glucose deprivation/reoxygenation (OGD/R) H9C2 cell model were selected to verify the main targets of the network pharmacological prediction. An intersectional analysis between Sal-B and MI/RI targets identified 69 common targets, with a PPI network analysis highlighting caspase-3, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) as central targets. GO and KEGG enrichment analyses indicated remarkable enrichment of the apoptosis pathway among these targets, suggesting their utility in experimental studies in vivo. Experimental results demonstrated that Sal-B treatment not only mitigated myocardial infarction size following MI/RI injury in mice but also modulated the expression of key apoptotic regulators, including Bcl-2-Associated X (Bax), caspase-3, JNK, and p38, alongside enhancing the B-cell lymphoma-2 (Bcl-2) expression, thereby inhibiting myocardial tissue apoptosis. This study leveraged an integrative network pharmacology approach to predict Sal-B's potential targets in MI/RI treatment and verified the involvement of key target proteins within the predicted signaling pathways through both in vivo and in vitro experiments, offering a comprehensive insight into Sal-B's pharmacological mechanism in MI/RI management. [ABSTRACT FROM AUTHOR]

Depression is a common psychiatric disorder that belongs to the category of ''Depression Syndrome'' in traditional Chinese medicine (TCM), and its etiology and pathogenesis are complex and unclear. It is characterized by high prevalence, high disability rate, and high recurrence rate, which seriously affect human health, and its treatment has become a research hotspot worldwide. At present, the antidepressants commonly used in the clinic are mainly Western medicine (WM), but there are problems such as frequent side effects and poor efficacy. Studies have found that the use of TCM prescriptions in the treatment of depression can achieve the same effect as WM; and when TCM prescriptions are combined with WM, the efficacy can be enhanced while the adverse effects of WM can be reduced. Pharmacological studies related to the treatment of depression with traditional Chinese medicine prescriptions (TCMPs) have focused on the neurobiochemical system, gut microbes, and energy metabolism in mitochondria. No one has yet reviewed the pharmacological mechanism of TCMPs for depression. So, this paper reviews the pharmacological mechanism of TCMPs for depression from the perspective of TCMPs, introduces the progress of research on classical TCMPs for depression and their antidepressant mechanism. This article aims to promote the application of TCMPs in the clinic and provide a new therapeutic idea for the clinical treatment of depression.

Puerarin, a monomer of traditional Chinese medicine, is a key component of Pueraria radix. Both clinical and experimental researches demonstrated that puerarin has therapeutic effects on Parkinson's disease (PD). Puerarin's pharmacological mechanisms include: 1) Anti-apoptosis. Puerarin inhibits cell apoptosis through the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. Puerarin also exerts a hormone-like effect against cell apoptosis; 2) Anti-oxidative stress injury. Puerarin inhibits the Nrf2 nuclear exclusion through the GSK-3β/Fyn pathway to promote the Nrf2 accumulation in the nucleus, and then promotes the antioxidant synthesis through the Nrf2/ARE signaling pathway to protect against oxidative stress; 3) Neuroprotective effects by intervening in the ubiquitin-proteasome system (UPS) and autophagy-lysosomal pathway (ALP). Puerarin significantly enhances the activity of chaperone-mediated autophagy (CMA), which downregulates the expression of α-synuclein, reduces its accumulation, and thus improves the function of damaged neurons. Additionally, puerarin increases proteasome activity and decreases ubiquitin-binding proteins, thereby preventing toxic accumulation of intracellular proteins; 4) Alleviating inflammatory response. Puerarin inhibits the conversion of microglia to the M1 phenotype while inducing the transition of microglia to the M2 phenotype. Furthermore, puerarin promotes the secretion of anti-inflammatory factor and inhibits the expression of pro-inflammatory factors; 5) Increasing the levels of dopamine and its metabolites. Puerarin could increase the levels of dopamine, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum; 6) Promoting neurotrophic factor expression and neuronal repair. Puerarin increases the expression of glial cell-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), thereby exerting a neuroprotective effect. Moreover, the regulation of the gut microbiota by puerarin may be a potential mechanism for the treatment of PD. The current review discusses the molecular mechanisms of puerarin, which may provide insight into the active components of traditional Chinese medicine in the treatment of PD.

Matrine (MT) and Oxymatrine (OMT) are two natural alkaloids derived from plants. These bioactive compounds are notable for their diverse pharmacological effects and have been extensively studied and recognized in the treatment of cardiovascular diseases in recent years. The cardioprotective effects of MT and OMT involve multiple aspects, primarily including antioxidative stress, anti-inflammatory actions, anti-atherosclerosis, restoration of vascular function, and inhibition of cardiac remodeling and failure. Clinical pharmacology research has identified numerous novel molecular mechanisms of OMT and MT, such as JAK/STAT, Nrf2/HO-1, PI3 K/AKT, TGF-β1/Smad, and Notch pathways, providing new evidence supporting their promising therapeutic potential against cardiovascular diseases. Thus, this review aims to investigate the potential applications of MT and OMT in treating cardiovascular diseases, encompassing their mechanisms, efficacy, and safety, confirming their promise as lead compounds in anti-cardiovascular disease drug development.

Lung cancer is a prevalent malignant tumor and a leading cause of cancer-related fatalities globally. However, current treatments all have limitations. Therefore, there is an urgent need to identify a readily available therapeutic agent to counteract lung cancer development and progression. Luteolin is a flavonoid derived from vegetables and herbs that possesses preventive and therapeutic effects on various cancers. With the goal of providing new directions for the treatment of lung cancer, we review here the recent findings on luteolin so as to provide new ideas for the development of new anti-lung cancer drugs. The search focused on studies published between January 1995 and January 2024 that explored the use of luteolin in lung cancer. A comprehensive literature search was conducted in the SCOPUS, Google Scholar, PubMed, and Web of Science databases using the keywords ''luteolin'' and ''lung cancer.'' By collecting previous literature, we found that luteolin has multiple mechanisms of therapeutic effects, including promotion of apoptosis in lung cancer cells; inhibition of tumor cell proliferation, invasion and metastasis; and modulation of immune responses. In addition, it can be used as an adjuvant to radio-chemotherapy and helps to ameliorate cancer complications. This review summarizes the structure, natural sources, physicochemical properties and pharmacokinetics of luteolin, and focuses on the anti-lung cancer mechanism of luteolin, so as to provide new ideas for the development of new anti-lung cancer drugs.

The morbidity and mortality of malignant tumors are progressively rising on an annual basis. Traditional Chinese Medicine (TCM) holds promise as a possible therapeutic agent for the avoidance or therapy of malignant tumors. Salvia miltiorrhiza Bunge (Danshen), a traditional Asian functional food, has therapeutic characteristics in application for the treatment of malignant tumors. Dihydrotanshinone I (DHTS) is the principal lipophilic phenanthraquinone compound found in Salvia miltiorrhiza Bunge, whose anti-tumor effect has attracted widespread attention. The anti-tumor effects include inhibiting cancer cell proliferation, triggering apoptosis of tumor cells, inducing ferroptosis in tumor cells, inhibiting tumor cell invasion and metastasis, and improving drug resistance of tumor cells. In this paper, we summarized and analyzed the mechanisms and targets of anti-tumor effect of DHTS, providing new ideas and establishing a solid theoretical basis for the future advancement and clinical treatment of DHTS.

Abstract Mangiferin (MAN) was a natural bioactive xanthone with remarkable antioxidative, anti‐inflammatory, and antiapoptotic effects. The purpose of this study to determine the protective influence of MAN on D‐galactose (D‐gal)‐induced aging and cognitive impairment, together with its underlying molecular mechanism. The network pharmacology molecular docking analysis revealed that MAN has a potential binding with aging‐related oxidative stress and apoptosis proteins. In D‐gal‐induced aging mice, MAN could significantly reduce D‐gal‐induced histopathological changes of liver and brain tissues. Moreover, MAN administration obviously increased activities of antioxidant enzymes (SOD, T‐AOC, GSH‐Px, and CAT) and decreased levels of AChE and MDA in the serum, liver, or brain tissues. Additionally, MAN alleviated learning and memory disorders and improved the exploration ability. Western blotting and immunohistochemical analysis results revealed that MAN could regulate the expressions of PI3K/Akt/Nrf2 signaling pathway‐related proteins and apoptotic‐related proteins (Bax, Bcl‐2, and Caspase‐9) in the liver tissues. Therefore, these findings suggested that MAN can be used as a potent dietary supplement in functional foods for the protection against aging‐related impairments.

Ganoderma lucidum (G. lucidum) is a traditional edible and medicinal mushroom in China. The main bioactive components in G. lucidum include triterpenoids, polysaccharides, steroids, and sterols. Ganoderic acids (GAs) are one of the most abundant triterpenoids found in G. lucidum, garnering significant attention from researchers in the fields of medicine and health care. We summarize the extensive studies on the physiological function of GAs in anti-cancer, anti-inflammatory, radiation protection, anti-aging, liver protection, anti-microbial, and neuroprotection areas, among others. This review provides a comprehensive overview of the recent advances in the bioactivities and pharmacological mechanisms of GAs, aiming to delineate the current research directions and the state of the art in this field. This analysis helps to rapidly identify new bioactivities of GAs and understand their mechanisms, leading to more effective treatments for various diseases.

Vascular endothelial injury is the initiating factor in atherosclerosis Currently, western medical treatment is ineffective and has many adverse effects. It has been found that flavonoids, the active ingredients of Chinese medicine, can regulate endothelial cell function by reducing inflammation, inhibiting oxidative stress, improving apoptosis and autophagy. They have the advantages of multiple pathways, links and targets in the prevention and treatment of atherosclerosis, and have great potential for development. This paper reviewed the recent studies on the mechanism of flavonoids in improving endothelial injury, and provided reference and theoretical basis to promote the discovery of new drug candidates for vascular endothelial injury and the wide application of flavonoids. [ABSTRACT FROM AUTHOR]

Introduction: Huangkui capsule (HKC) is made from the ethanol extract of Abelmoschus manihot (L.) Medik [Malvaceae; abelmoschi corolla] and received approval from the China Food and Drug Administration (Z19990040) in 1999. Currently, HKC is used for treatment of the patients with diabetic nephropathy (DN) in China. The bioactive chemical constituents in HKC are total flavonoids of A. manihot (L.) Medik (TFA). The present study aims to identify the primary flavonoid metabolites in HKC and TFA and their metabolism fates in db/db mice, the animal model for the study of type 2 diabetes and DN. Methods: HKC (0.84 g/kg/d) and TFA (0.076 g/kg/d) or vehicle were respectively administered daily via oral gavage in db/db mice for 4 weeks. The metabolism fate of the main metabolites of HKC in serum, liver, kidney, heart, jejunum, colon, jejunal contents, colonic contents, and urine of db/db mice were analyzed with a comprehensive metabolite identification strategy. Results and Discussion: In db/db mice administered with HKC and TFA, 7 flavonoid prototypes and 38 metabolites were identified. The related metabolic pathways at Phases I and II reactions included dehydroxylation, deglycosylation, hydrogenation, methylation, glucuronidation, sulphation, and corresponding recombined reactions. Quercetin, isorhamnetin, quercetin sulphate, quercetin monoglucuronide, and isorhamnetin monoglucuronide presented a high exposure in the serum and kidney of db/db mice. Thereby, the present study provides a pharmacodynamic substance basis for better understanding the mechanism of A. manihot (L.) Medik for medication of DN. [ABSTRACT FROM AUTHOR]

The incidence rate of depression, a mental disorder, is steadily increasing and has the potential to become a major global disability factor. Given the complex pathological mechanisms involved in depression, the use of conventional antidepressants may lead to severe complications due to their side effects. Hence, there is a critical need to explore the development of novel antidepressants. Ferroptosis, a newly recognized form of cell death, has been found to be closely linked to the onset of depression. Several studies have indicated that certain active ingredients can ameliorate depression by modulating the ferroptosis signaling pathway. Notably, traditional Chinese medicine (TCM) active ingredients and TCM prescriptions have demonstrated promising antidepressant effects in previous investigations owing to their unique advantages in antidepressant therapy. Building upon these findings, our objective was to review recent relevant research and provide new insights and directions for the development and application of innovative antidepressant strategies. [ABSTRACT FROM AUTHOR]

Silibinin capsules are a kind of hepatoprotective drugs made from silymarin, the main ingredient in silybin. This paper reviews the pharmacological characteristics and quality of Silibinin capsules at home and abroad in recent years, and mainly discusses from the dimensions of pharmacological mechanism, clinical application, pharmacokinetics, safety and quality standards, so as to provide references for the rational use of Silibinin capsules in clinic. [ABSTRACT FROM AUTHOR]

Cannabinoids interact with Cannabinoid Receptors (CBRs) and some related non-cannabinoid transcription factors within neurological and non-neuronal-specific receptors. The current review has covered pharmacological molecular mechanisms during an epileptic attack and provided a beneficial therapeutic approach for the treatment of neurological disorders. CBRs and new targets may be involved in Cannabidiol (CBD) effects. Although it has a low affinity for both CB1 and CB2 receptors, CBD can effectively block CB1 receptors when concentrations are high. The following are numerous potential CBD goals: (A) Blocking GPR55 receptors; (B) Systematic desensitization of TRPV1 channels; (C) Suppressing adenosine re-uptake transporters; (D) Regulating GABA production; and (E) Influencing the Endocannabinoid networks. According to the current review, numerous outstanding cannabis formulations are currently being developed and proven in numerous clinical studies. Nevertheless, more research is urgently needed to determine the best dosage and proportions of cannabinoids for reducing seizure frequency. This study needs to take place in huge, rising randomized clinical trials that really can reveal the rewards and drawbacks of cannabinoids in controlled patients. Furthermore, there is a lot of significant variation in the experimental approaches performed, particularly when it comes to the length of immunosuppressive drugs, dosages, and delivery methods in animal models. So, reproducing the existing results using comparable methods will be one of the biggest challenges in the additional investigation. [ABSTRACT FROM AUTHOR]

(1) Background: Diabetic cardiomyopathy (DCM) is a unique form of cardiomyopathy that develops as a consequence of diabetes and significantly contributes to heart failure in patients. Esaxerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has demonstrated potential in reducing the incidence of cardiovascular and renal events in individuals with chronic kidney and diabetes disease. However, the exact protective effects of esaxerenone in the context of DCM are still unclear. (2) Methods: The DCM model was successfully induced in mice by administering streptozotocin (55 mg/kg per day) for five consecutive days. After being fed a normal diet for 16 weeks, echocardiography was performed to confirm the successful establishment of the DCM model. Subsequent sequencing and gene expression analysis revealed significant differences in gene expression in the DCM group. These differentially expressed genes were identified as potential targets for DCM. By utilizing the Swiss Target Prediction platform, we employed predictive analysis to identify the potential targets of esaxerenone. A protein–protein-interaction (PPI) network was constructed using the common targets of esaxerenone and DCM. Enrichment analysis was conducted using Metascape. (3) Results: Compared to the control, the diabetic group exhibited impaired cardiac function and myocardial fibrosis. There was a total of 36 common targets, with 5 key targets. Enrichment analysis revealed that the chemokine and PI3K-Akt signaling pathway was considered a crucial pathway. A target-pathway network was established, from which seven key targets were identified. All key targets exhibited good binding characteristics when interacting with esaxerenone. (4) Conclusion: The findings of this study suggest that esaxerenone exhibits a favorable therapeutic effect on DCM, primarily by modulating the chemokine and PI3K-Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Sinomenine (SIN), an alkaloid derived from the traditional Chinese medicine, Caulis Sinomenii, has been used as an anti-inflammatory drug in China for over 30 years. With the continuous increase in research on the pharmacological mechanism of SIN, it has been found that, in addition to the typical rheumatoid arthritis (RA) treatment, SIN can be used as a potentially effective therapeutic drug for anti-tumour, anti-renal, and anti-nervous system diseases. By reviewing a large amount of literature and conducting a summary analysis of the literature pertaining to the pharmacological mechanism of SIN, we completed a review that focused on SIN, found that the current research is insufficient, and offered an outlook for future SIN development. We hope that this review will increase the public understanding of the pharmacological mechanisms of SIN, discover SIN research trial shortcomings, and promote the effective treatment of immune diseases, inflammation, and other related diseases.

Zhiqiang Shi,1 Yu Liu,1,2 Xiaodan Chang,3 Yuan Gao,4 Min Hao,1 Shuo Feng,1 Haoyu Dong1 1Department of Traditional Chinese Medicine Surgery, College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine Surgery, College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 3Department of Dermatology, Hohhot Second Hospital, Hohhot, People’s Republic of China; 4Department of Anorectal Diseases, Inner Mongolia Hospital of Traditional Chinese Medicine, Hohhot, People’s Republic of ChinaCorrespondence: Yu Liu, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot, Inner Mongolia, People’s Republic of China, Tel +86-153-3471-2606, Email 15074930848@163.comPurpose: This paper aims to investigate the effect of Tounong San (TNS), a well-known traditional Chinese medicine prescription for suppurative infections, on the immune function.Methods: A suppurative infection model was established by injecting Staphylococcus aureus into subcutaneous tissue on the backs of rats. The expressions of CD68, CD163, CD31 and MPO in abscess tissues, phagocytosis rate and reactive oxygen species (ROS) of neutrophils in blood, phagocytosis function of peritoneal macrophages, and proliferation of blood lymphocytes, expression of IL-1, IL-6, CH50, TNF-α, IFN-γ, IgG, IgM in serum were detected at different time points.Results: On the 3rd day of medication, fibrinogen wrapped around the abscesses was visible in TNS groups, with an increase in new blood vessels and the expression of a large number of macrophages and neutrophils. On the 6th day, the pus of TNS groups diminished, and the number of new blood vessels reached its peak. On the 9th day, the abscesses disappeared in TNS groups, fewer new blood vessels, macrophages, and neutrophils were expressed, and more fibrocytes appeared and filled the original pus cavities. On the 3rd and 9th day of medication, the phagocytic rates of neutrophils and macrophages were significantly improved in TNS group, and the ROS content of neutrophils was increased on the 9th day. TNS has no effect on lymphocyte proliferation in vitro, but it can regulate the secretion of IgG and IgM by lymphocytes. TNS increases the level of IL-1, decreases the levels of IL-6 and TNF-α, and regulates the expressions of IFN-γ and CH50 in two ways.Conclusion: TNS can form fibrinogen-wrapped pus to prevent bacterial infection from going deeper, and to improve the phagocytic function of phagocytes, the secretion of lymphocytes, and the defense function of the complement system. Therefore, it is a competitive drug for the treatment of suppurative diseases.Keywords: Tounong San, suppurative infection, immune function, pharmacological mechanism

Zhichao Xing,1,&ast; Anping Su,1,&ast; Li Mi,1 Yujie Zhang,1 Ting He,1 Yuxuan Qiu,2 Tao Wei,1 Zhihui Li,1 Jingqiang Zhu,1 Wenshuang Wu1 1Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingqiang Zhu; Wenshuang Wu, Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China, Email zhujingqiang@scu.edu.cn; wenshuang_wu@163.comAbstract: Cancer, as the leading cause of death worldwide, poses a serious threat to human health, making the development of effective tumor treatments a significant challenge. Natural products continue to serve as crucial resources for drug discovery. Among them, Withaferin A (WA), the most active phytocompound extracted from the renowned dietary supplement Withania somnifera (L.) Dunal, exhibits remarkable anti-tumor efficacy. In this manuscript, we aim to comprehensively summarize the pharmacological characteristics of WA as a potential anti-tumor drug candidate, with the objective of contributing to its further development and the discovery of prospective drugs. Through an extensive review of literature from PubMed, Science Direct, and Web of Science, we have gathered substantial evidence showcasing WA’s significant anti-tumor effects against a wide range of cancers in both in vitro and in vivo studies. Mechanistically, WA exerts its anti-tumor influence by inducing cell cycle arrest, apoptosis, autophagy, and ferroptosis. Additionally, it inhibits cell proliferation, cancer stem cells, tumor metastasis, and also suppresses epithelial-mesenchymal transition (EMT) and angiogenesis. Several studies have identified direct target proteins of WA, such as vimentin, Hsp90, annexin II and mFAM72A, while BCR-ABL, Mortalin (mtHsp70), Nrf2, and c-MYB are potential targets of WA. Notwithstanding its remarkable anti-tumor efficacy, there are some limitations associated with WA, including potential toxicity and poor oral bioavailability, which need to be addressed when considering it as an anti-tumor candidate agent. Nevertheless, I given its promising anti-tumor attributes, WA remains an encouraging candidate for future drug development. Unveiling the exact target and comprehensive mechanism of WA’s action represents a crucial research direction to pursue in the future.Graphical Abstract: Keywords: Withaferin A, Withania somnifera, dietary supplement, anti-cancer activity, pharmacological mechanism, direct target

Abstract Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with a high morbidity and mortality rate. Exogenous vitamin C supplementation is a potential therapeutic option for the treatment of multi-organ dysfunction in sepsis due to the significantly lower levels of vitamin C in the circulating blood of sepsis patients compared to healthy subjects and the importance of vitamin C in many of the physiological processes of sepsis. Vitamin C may influence the function of numerous organs and systems, including the heart, lungs, kidneys, brain, and immune defences, by reducing oxidative stress, inhibiting inflammatory factor surges, regulating the synthesis of various mediators and hormones, and enhancing immune cell function. With the development of multiple clinical randomized controlled trials, the outcomes of vitamin C treatment for critically ill patients have been discussed anew. This review's objectives are to provide an overview of how vitamin C affects various organ functions in sepsis and to illustrate how it affects each organ. Understanding the pharmacological mechanism of vitamin C and the organ damage caused by sepsis may help to clarify the conditions and clinical applications of vitamin C.

Objective:To analyze the main target genes, key pathways and their mechanisms of action of resveratrol in the treatment of early hepatocellular carcinoma based on multiple databases using a network pharmacology approach.Method:The targets of resveratrol was obtained from the Swiss Target Prediction database; the targets of early hepatocellular carcinoma were obtained from the GeneCards, OMIM and DisGent databases. The compound-target-disease network was constructed using Cytoscape software; the protein interaction network was constructed using STRING database; GO function and KEGG pathway enrichment analysis were performed in R language.Results:Sixty-nine potential targets for resveratrol were obtained through the Swiss Target Prediction database. Searching and de-duplicating the disease database yielded 9682 disease targets for early hepatocellular carcinoma. Seven hundred and fifty four entries were obtained from GO functional enrichment analysis and 99 statistically significant pathways were obtained from KEGG enrichment analysis.Conclusion:The mechanism of action of resveratrol for early hepatocellular carcinoma is a multi-target, multi-pathway interaction. The receptors may be related to SRC, CYP3A4, PIK3CA, CYP1A1, RELA, ESR1 and other targets, and the major signalling pathways may be related to Ovarian steroidogenesis, steroid hormone biosynthesis, chemical carcinogenesis-receptor activation, endocrine resistance, chemical carcinogenesis-DNA adducts, nitrogen metabolism, hepatocellular carcinoma, etc. It provides a theoretical basis for the next in-depth experimental study.

The effectiveness and safety of traditional Chinese medicine's active ingredients in anti-tumor effects have attracted widespread attention worldwide. Solasonine is the main anti-tumor component of the traditional Chinese medicine Solanum nigrum L, which can inhibit tumor cell proliferation, induce apoptosis, induce ferroptosis in tumor cells, and inhibit of tumor cell metastasis, thereby inhibiting tumor progression. Therefore, we summarized anti-tumor mechanisms and targets of solasonine to provide new ideas and theoretical basis for its further development and application.

Depression is characterized by prominent indicators and manifestations, such as anhedonia, which refers to the inability to experience pleasure, and persistent feelings of hopelessness. In clinical practice, the primary treatment approach involves the utilization of selective serotonin reuptake inhibitors (SSRIs) and related pharmacological interventions. Nevertheless, it is crucial to recognize that these agents are associated with significant adverse effects. Traditional Chinese medicine (TCM) adopts a multifaceted approach, targeting diverse components, multiple targets, and various channels of action. TCM has potential antidepressant effects. Anomalies in adult hippocampal neurogenesis (AHN) constitute a pivotal factor in the pathology of depression, with the regulation of AHN emerging as a potential key measure to intervene in the pathogenesis and progression of this condition. This comprehensive review presented an overview of the pharmacological mechanisms underlying the antidepressant effects of active ingredients found in TCM. Through examination of recent studies, we explored how these ingredients modulated AHN. Furthermore, we critically assessed the current limitations of research in this domain and proposed novel strategies for preclinical investigation and clinical applications in the treatment of depression in future.

Cardiovascular disease (CVD) remains the leading cause of death and disability globally. A wide range of CVDs have been reported, each of which diverges significantly, exhibiting sophisticated types of pathogenesis (e.g., inflammatory, oxidative stress, and disorders in cardiomyocyte metabolism). Compared with conventional treatments in modern medicine, traditional Chinese medicine (TCM) can exhibit comparative advantages in the treatment of CVDs. TCM can be utilized to develop effective strategies for addressing the challenges of CVD, with fewer side effects and higher therapeutic efficiency. Astragaloside IV (AS-IV) has been confirmed as one of the major active ingredients found in Astragalus membranaceus (a Chinese herbal medicine that has been extensively employed clinically for the treatments of CVDs). Since recent studies have shown that AS-IV in CVD treatments has achieved promising results, the substance has aroused great attention and further discussions in the field. The present review aims to summarize the recent pharmacological advances in employing AS-IV in the treatment of CVDs.

Lipid-lowering therapy is an important tool for the treatment of lipid metabolic diseases, which are increasing in prevalence. However, the failure of conventional lipid-lowering drugs to achieve the desired efficacy in some patients, and the sideeffects of these drug regimens, highlight the urgent need for novel lipid-lowering drugs. The liver and intestine are important in the production and removal of endogenous and exogenous lipids, respectively, and have an important impact on circulating lipid levels. Elevated circulating lipids predisposes an individual to lipid deposition in the vascular wall, affecting vascular function. Berberine (BBR) modulates liver lipid production and clearance by regulating cellular targets such as cluster of differentiation 36 (CD36), acetyl-CoA carboxylase (ACC), microsomal triglyceride transfer protein (MTTP), scavenger receptor class B type 1 (SR-BI), low-density lipoprotein receptor (LDLR), and ATP-binding cassette transporter A1 (ABCA1). It influences intestinal lipid synthesis and metabolism by modulating gut microbiota composition and metabolism. Finally, BBR maintains vascular function by targeting proteins such as endothelial nitric oxide synthase (eNOS) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). This paper elucidates and summarizes the pharmacological mechanisms of berberine in lipid metabolic diseases from a multi-organ (liver, intestine, and vascular system) and multi-target perspective. [ABSTRACT FROM AUTHOR]

Angiogenesis is the process by which new blood vessels form and is required for tumour growth and metastasis. It helps in supplying oxygen and nutrients to tumour cells and plays a crucial role in the local progression and distant metastasis of, and development of treatment resistance in, breast cancer. Tumour angiogenesis is currently regarded as a critical therapeutic target; however, anti‐angiogenic therapy for breast cancer fails to produce satisfactory results, owing to issues such as inconsistent efficacy and significant adverse reactions. As a result, new anti‐angiogenic drugs are urgently needed. Flavonoids, a class of natural compounds found in many foods, are inexpensive, widely available, and exhibit a broad range of biological activities, low toxicity, and favourable safety profiles. Several studies find that various flavonoids inhibit angiogenesis in breast cancer, indicating great therapeutic potential. In this review, we summarize the role of angiogenesis in breast cancer and the potential of natural flavonoids as anti‐angiogenic agents for breast cancer treatment. We discuss the value and significance of nanotechnology for improving flavonoid absorption and utilization and anti‐angiogenic effects, as well as the challenges of using natural flavonoids as drugs. [ABSTRACT FROM AUTHOR]

The antitumor effects of traditional drugs have received increasing attention and active antitumor components extracted from traditional drugs have shown good efficacy with minimal adverse events. Cepharanthine(CEP for short) is an active component derived from the Stephania plants of Menispermaceae, which can regulate multiple signaling pathways alone or in combination with other therapeutic drugs to inhibit tumor cell proliferation, induce apoptosis, regulate autophagy, and inhibit angiogenesis, thereby inhibiting tumor progression. Therefore, we retrieved studies concerning CEP's antitumor effects in recent years and summarized the antitumor mechanism and targets, in order to gain new insights and establish a theoretical basis for further development and application of CEP.

Ellagic acid (EA) is a kind of polyphenol compound extracted from a variety of herbs, such as paeoniae paeoniae, raspberry, Chebule, walnut kernel, myrrh, loquat leaf, pomegranate bark, quisquite, and fairy herb. It has anti-tumor, anti-oxidation, anti-inflammatory, anti-mutation, anti-bacterial, anti-allergic and multiple pharmacological properties. Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors, mainly through inducing tumor cell apoptosis, inhibiting tumor cell proliferation, inhibiting tumor cell metastasis and invasion, inducing autophagy, affecting tumor metabolic reprogramming and other forms of anti-tumor efficacy. Its molecular mechanism is mainly reflected in inhibiting the proliferation of tumor cells through VEGFR-2 signaling pathway, Notch signaling pathway, PKC signaling pathway and COX-2 signaling pathway. PI3K/Akt signaling pathway, JNK (cJun) signaling pathway, mitochondrial pathway, Bcl-2 / Bax signaling pathway, TGF-β/Smad3 signaling pathway induced apoptosis of tumor cells and blocked EMT process and MMP SDF1α/CXCR4 signaling pathway inhibits the metastasis and invasion of tumor cells, induces autophagy and affects tumor metabolic reprogramming to produce anti-tumor effects. At present, the analysis of the anti-tumor mechanism of ellagic acid is slightly lacking, so this study comprehensively searched the literature on the anti-tumor mechanism of ellagic acid in various databases, reviewed the research progress of the anti-tumor effect and mechanism of ellagic acid, in order to provide reference and theoretical basis for the further development and application of ellagic acid.

Objective: Epimedium (EPI) is a common Chinese herb with neuroprotective effects against a variety of central nervous system disorders, especially spinal cord injury (SCI). In this study, we performed network pharmacology and molecular docking analyses to reveal the mechanism underlying EPI treatment of SCI, then validated its efficacy using animal models. Methods: The active ingredients and targets of EPI were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and their targets annotated on the UniProt platform. SCI-related targets were searched from OMIM, TTD, and GeneCards databases. We employed the STRING platform to construct a protein-protein interaction (PPI) network then visualized the results using Cytoscape (3.8.2) software. We also subjected key EPI targets to ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, then docked the main active ingredients with the key targets. Finally, we established an SCI rat model to evaluate efficacy of EPI in treating SCI and validate the effects of different biofunctional modules predicted by network pharmacology. Results: A total of 133 EPI targets were associated with SCI. GO terms and KEGG pathway enrichment results showed that EPI's effect in treating SCI was significantly associated with inflammatory response, oxidative stress and the PI3K/AKT signaling pathway. Molecular docking results indicated that EPI's active ingredients have a high affinity for the key targets. Results from animal experiments revealed that EPI not only markedly improved Basso, Beattie, and Bresnahan scores in SCI rats, but also significantly improved p-PI3K/PI3K and p-AKT/AKT ratio. Moreover, EPI treatment not only mediated a significant decrease in malondialdehyde (MDA) but also increased both superoxide dismutase (SOD), and glutathione (GSH). However, this phenomenon was successfully reversed by LY294002, a PI3K inhibitor. Conclusion: EPI improves behavioral performance in SCI rats through anti-oxidative stress, which may be mediated by activation of the PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with a high morbidity and mortality rate. Exogenous vitamin C supplementation is a potential therapeutic option for the treatment of multi-organ dysfunction in sepsis due to the significantly lower levels of vitamin C in the circulating blood of sepsis patients compared to healthy subjects and the importance of vitamin C in many of the physiological processes of sepsis. Vitamin C may influence the function of numerous organs and systems, including the heart, lungs, kidneys, brain, and immune defences, by reducing oxidative stress, inhibiting inflammatory factor surges, regulating the synthesis of various mediators and hormones, and enhancing immune cell function. With the development of multiple clinical randomized controlled trials, the outcomes of vitamin C treatment for critically ill patients have been discussed anew. This review's objectives are to provide an overview of how vitamin C affects various organ functions in sepsis and to illustrate how it affects each organ. Understanding the pharmacological mechanism of vitamin C and the organ damage caused by sepsis may help to clarify the conditions and clinical applications of vitamin C. [ABSTRACT FROM AUTHOR]

Osteoporosis and osteoarthritis are common clinical aging-related bone metabolism disease, and their incidence gradually increases with age. Polydatin is a natural polyphenol and non-flavonoid compound present in the traditional Chinese medicine Polygonum cuspidatum, and it has attracted much attention because of its strong role in regulating bone metabolism and stimulating blood vessel formation. In this research, we summarize relevant literature that published at home or abroad, which contents about the characteristics of pharmacokinetic, pharmacological mechanisms and targets of polydatin in the prevention and treatment of osteoporosis and osteoarthritis. It is expected to provide more clues for the follow-up research on the prevention and treatment of aging-related bone metabolism diseases, and to supply more scientific theoretical basis for the development and utilization of polydatin. [ABSTRACT FROM AUTHOR]

Introduction: The gastric mucosa (GM) is the first barrier and vital interface in the stomach that protects the host from hydrochloric acid in gastric juice and defends against exogenous insults to gastric tissues. The use of traditional Chinese medications (TCMs) for the treatment of gastric mucosal injury (GMI) has longstanding history and a good curative effect. Whereas there are poor overall reports on the intrinsic mechanisms of these TCM preparations that pharmacology uses to protect body from GMI, which is crucial to treating this disease. These existing reviews have deficiencies that limit the clinical application and development of both customary prescriptions and new drugs. Methods: Further basic and translational studies must be done to elucidate the intrinsic mechanisms of influence of these TCM preparations. Moreover, welldesigned and well-conducted experiences and clinical trials are necessary to ascertain the efficacy and mechanisms of these agents. Therefore, this paper presents a focused overview of currently published literature to assess how TCMs action that facilitates the cures for GMI. It offers a whole train of current state of pharmacological evidence, identifies the pharmacological mechanisms of TCMs on GM, and highlights that remarkable capacity of TCMs to restore GM after damage. Results: These TCMs preparations promote the repair of multicomponent targets such as the gastric mucus, epithelial layer, blood flow (GMBF) and lamina propria barrier. Summary: Overall, this study has summarized the essential regulatory mechanisms and pharmacological efficacy of TCMs on new and productive therapeutic targets. Discussion: This review provides an avenue for studying various drugs with potentially promising effects on mucosal integrity, as well as subsequent pharmacological studies, clinical applications, and new drug development. [ABSTRACT FROM AUTHOR]

Metformin is a traditional antidiabetic drug that also shows potential antitumor effects in cervical cancer. However, some of its apoptosis-related mechanisms are still unclear. In this study, flow cytometry, western blotting, and RNA sequencing (RNA-seq) were used to evaluate the molecular mechanisms of metformin in HeLa cells. The results showed that metformin inhibited cell viability and promoted apoptosis, the protein expression level of Caspase-3 (CASP3) was increased and that of BCL-2 was decreased in HeLa cells treated with metformin. The RNA-seq results indicated a total of 239 differentially expressed genes between the metformin and control check (CK) groups, with 136 genes upregulated and 103 genes downregulated, and 14 of them were found to be associated with apoptosis signaling pathways. The DDIT3 and HRK genes were robustly upregulated in HeLa cells by the endoplasmic reticulum (ER) stress and the mitochondrial pathway of apoptosis. Metformin also affects the expression of PPP2R5C, PPP2R5A, and RRAGA, which participate in biological processes such as PI3K-AKT, mTOR, and AMPK signaling pathways. Metformin mediates the expression of related genes to induce apoptosis. [ABSTRACT FROM AUTHOR]

Curcumin, a well-known hydrophobic polyphenol extracted from the rhizomes of turmeric (Curcuma longa L.), has attracted great interest in the last ten years due to its multiple pharmacological activities. A growing body of evidence has manifested that curcumin has extensive pharmacological activities including anti-inflammatory, anti-oxygenation, lipid regulation, antiviral, and anticancer with hypotoxicity and minor adverse reactions. However, the disadvantages of low bioavailability, short half-life in plasma, low drug concentration in blood, and poor oral absorption severely limited the clinical application of curcumin. Pharmaceutical researchers have carried out plenty of dosage form transformations to improve the druggability of curcumin and have achieved remarkable results. Therefore, the objective of this review summarizes the pharmacological research progress, problems in clinical application and the improvement methods of curcumin's druggability. By reviewing the latest research progress of curcumin, we believe that curcumin has a broad clinical application prospect for its wide range of pharmacological activities with few side effects. The deficiencies of lower bioavailability of curcumin could be improved by dosage form transformation. However, curcumin in the clinical application still requires further study regarding the underlying mechanism and clinical trial verification. [ABSTRACT FROM AUTHOR]

Background and Objectives: Aucklandiae Radix is a well-known medicinal herb that is often used to treat gastric ulcer, but its molecular mechanism of anti-ulcer action is poorly understood. This research aimed to reveal the potential active components, core targets, and mechanisms of Aucklandiae Radix in treating gastric ulcer by combining network pharmacology and animal experimentation. Materials and Methods: First, a network pharmacology strategy was used to predict the main components, candidate targets, and potential signaling pathways. Molecular docking was then used to confirm the binding affinity between the main components and primary targets. Finally, rats were treated with indomethacin 30 mg/kg to establish a gastric ulcer model. Aucklandiae Radix extract (0.15, 0.3, and 0.6 g/kg) was pre-treated in rats by oral gavage for 14 days, and the protective effect and candidate targets of network pharmacology were validated through morphological observation, pathological staining, and biochemical index detection. Results: A total of eight potential active components and 331 predicted targets were screened from Aucklandiae Radix, 37 of which were common targets with gastric ulcer. According to the component–target network and protein-protein interaction (PPI) network, stigmasterol, mairin, sitosterol, and dehydrocostus lactone were identified as the key components, and RAC-alpha serine/threonine-protein kinase (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), interleukin 1 beta (IL1B), caspase-3 (CASP3), and CASP8 were selected as the core targets. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment results revealed the pharmacological mechanism of Aucklandiae Radix against gastric ulcer related to many biological processes and pathways, including antibacterial, anti-inflammatory, prostaglandin receptor response, and apoptosis. Molecular docking verification showed that the key components and core targets had good binding affinities. In the in vivo experiments, Aucklandiae Radix notably relieved the gastric ulcer by reducing the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and myeloperoxidase (MPO) while improving the gastric histopathological features. Conclusion: The overall findings suggest that Aucklandiae Radix treats gastric ulcer with a multi-component, multi-target, and multi-mechanism model. [ABSTRACT FROM AUTHOR]

Objective: Based on network meta-analysis (NMA) and network pharmacology approaches, we explored the clinical efficacy of different regimens, and clarified the pharmacological mechanisms of N-butylphthalide (NBP) in the treatment of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods: Firstly, NMA was conducted to obtain the ranking of the efficacy of different regimens for the treatment of DEACMP. Secondly, the drug with a relatively high efficacy ranking was selected and its mechanism of treatment for DEACMP was identified through a network pharmacology analysis. By the use of protein interaction and enrichment analysis, the pharmacological mechanism was predicted, and molecular docking was subsequently carried out to verify the reliability of the results. Results: A total of 17 eligible randomized controlled trials (RCTs) involving 1293 patients and 16 interventions were eventually included in our analysis from NMA. Mesenchymal stem cells (MSCs) + NBP significantly increased mini-mental state examination (MMSE) and Barthel index (BI) scores; NBP + dexamethasone (DXM) was the most effective treatment in improving the activity of daily living (ADL) scores; NBP significantly decreased national institutes of health stroke scale (NIHSS) scores; Xingzhi-Yinao granules (XZYN) had more advantages in improving Montreal cognitive assessment (MoCA) scores, translational direct current stimulation (tDCS) had a significant effect in improving P300 latency and P300 amplitude and Kinnado + Citicoline had the most obvious effect in improving malondialdehyde (MDA). Meanwhile, by network pharmacology analysis, 33 interaction genes between NBP and DEACMP were obtained, and 4 of them were identified as possible key targets in the process of MCODE analysis. 516 Gene ontology (GO) entries and 116 Kyoto Encyclopedia of Gene and Genome (KEGG) entries were achieved by enrichment analysis. Molecular docking showed that NBP had good docking activity with the key targets. Conclusion: The NMA screened for regimens with better efficacy for each outcome indicator in order to provide a reference for clinical treatment. NBP can stably bind ALB, ESR1, EGFR, HSP90AA1, and other targets, and may play a role in neuroprotection for patients with DEACMP by modulating Lipid and atherosclerosis, IL-17 signaling pathway, MAPK signaling pathway, FoxO signaling pathway, PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) has a history of over 2000 years in treating infectious diseases, among which the clinical treatment of the common cold (colds) and influenza (flu) is the most widespread and well-established. It is difficult to tell the difference between a cold and the flu based on the symptoms alone. The flu vaccine protects against influenza, but there is no vaccine or specific medication to protect against the common cold. Due to the lack of a reliable scientific basis, TCM has not received sufficient attention in Western medicine. Therefore, we systematically evaluated the scientific evidence proving the efficacy of TCM intervention in treating colds for the first time by examining theoretical principles, clinical research, and pharmacological perspectives, as well as the mechanisms behind this efficacy. In TCM theory, there are four important external environmental factors that may cause a cold, which are called "cold, heat, dryness, and dampness". The scientific basis for this theory has been described and will help researchers to understand and recognize its importance. The results of the systematic review of high-quality randomized controlled clinical trials (RCTs) have shown that TCM is effective and safe for the treatment of colds. Therefore, TCM might be used as a complementary or alternative approach to cold treatment and management. Some clinical trials have demonstrated that TCM may have potential therapeutic effects in preventing colds and treating their sequelae. However, more high-quality, large-scale randomized controlled trials should be conducted in the future for further verification. Pharmacological studies have shown that active ingredients extracted from TCM for treating colds have antiviral, anti-inflammatory, immune-regulating, and anti-oxidative properties. We expect that this review will guide the optimization and rationalization of TCM clinical practice and scientific research in the treatment of colds. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to investigate the modular characteristics and mechanism of action of Chinese herbs for vascular calcification (VC) treatment. MATERIALS AND METHODS: Network pharmacology coupled with literature data mining was utilized to assess the Chinese herbal clinical performance as well as its similarity, characteristics, ingredient, target, and Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and network construction. RESULTS: The top 15 medications from the literature, according to the usage, and 190 active chemicals, 183 common targets between medication and VC-related targets were weeded out. Analysis of the relationships between the active ingredients, pharmacological targets, and signaling pathways helped to clearly define the therapeutic effect of Traditional Chinese Medicine (TCM). Importantly, we discovered seven most hub proteins (AKT1, CTNNB1, TNF, EGFR, TP53, JUN and IL-6) and two of the herbs' most fundamental ingredients (Formononetin and Luteolin) in TCM-mediated VC suppression. Mechanistically, the metabolic pathways [AGE-RAGE pathway, interleukin-17 (IL-17) pathway, and p53 pathway] as well as smooth muscle adaptation (functional remodeling) and oxidoreductase activity (redox homeostasis modulating) are also crucially implicated. CONCLUSIONS: Our work, accomplished by network pharmacology and data mining, increases our understanding of TCM in VC therapy and may offer insightful information for future drug discovery investigations. [ABSTRACT FROM AUTHOR]