Traditional Chinese medicine for functional gastrointestinal disorders and inflammatory bowel disease: narrative review of the evidence and potential mechanisms involving the brain-gut axis.

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.

Radix Astragali and Its Representative Extracts for Diabetic Nephropathy: Efficacy and Molecular Mechanism.

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-ß1/Smads, MAPK (ERK), p38/MAPK, JNK/MAPK, Wnt/ß-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.

Research progress on the regulatory and pharmacological mechanism of chemical components of Dendrobium.

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.

Potential mechanisms of rheumatoid arthritis therapy: Focus on macrophage polarization.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that affects multiple organs and systems in the human body, often leading to disability. Its pathogenesis is complex, and the long-term use of traditional anti-rheumatic drugs frequently results in severe toxic side effects. Therefore, the search for a safer and more effective antirheumatic drug is extremely important for the treatment of RA. As important immune cells in the body, macrophages are polarized. Under pathological conditions, macrophages undergo proliferation and are recruited to diseased tissues upon stimulation. In the local microenvironment, they polarize into different types of macrophages in response to specific factors and perform unique functions and roles. Previous studies have shown that there is a link between macrophage polarization and RA, indicating that certain active ingredients can ameliorate RA symptoms through macrophage polarization. Notably, Traditional Chinese medicine (TCM) monomer component and compounds demonstrate a particular advantage in this process. Building upon this insight, we reviewed and analyzed recent studies to offer valuable and meaningful insights and directions for the development and application of anti-rheumatic drugs.

Flavonoids Derived from Chinese Medicine: Potential Neuroprotective Agents.

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.

Exploring the potential mechanism of Chinese herbal medicine Fuzi on aplastic anemia based on UHPLC-MS/MS method combined with network pharmacology and molecular docking.

To reveal the potential mechanism of the effect of Chinese Herbal Medicine Fuzi on Aplastic anaemia (AA) according to the network pharmacology approach and molecular docking. According to Ultra High Performance Liquid Chromatography Mass Spectrometry (UHPLC-MS/MS), 146 chemical ingredients of Fuzi were obtained. By SwissADME online system analysis, a total of 55 compounds such as Magnoflorine, Scutellarein, Luteolin and Gingerol may be the main active components of Fuzi and 145 common targets related to AA were predicted. 17 targets such as MAPK1, AKT1 and GRB2 were considered as hub targets. KEGG and GO enrichment analysis obtained 122 signalling pathways and 950 remarkable results. These results suggested that Fuzi exerted pharmacological effects on AA mainly by regulating PI3K-Akt, MAPK and JAK-STAT signalling pathways and epithelial cell proliferation, cell differentiation, regulate energy production and other biological processes. Meanwhile, molecular docking results showed that the hub targets had good binding ability with the main active ingredients.

Shirebi granules ameliorate acute gouty arthritis by inhibiting NETs-induced imbalance between immunity and inflammation.

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.

Interplay between traditional Chinese medicine polysaccharides and gut microbiota: The elusive "polysaccharides-bond-bacteria-enzyme" equation.

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.

Progress of research on the treatment of depression by traditional Chinese medicine prescriptions.

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.

Salvianolic acid B in fibrosis treatment: a comprehensive review.

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 anti-fibrotic 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.

The role of gastrodin in the management of CNS-related diseases: Underlying mechanisms to therapeutic perspectives.

Central nervous system (CNS)-related diseases have a high mortality rate, are a serious threat to physical and mental health, and have always been an important area of research. Gastrodin, the main active metabolite of Gastrodia elata Blume, used in Chinese medicine and food, has a wide range of pharmacological effects, mostly related to CNS disorders. This review aims to systematically summarize and discuss the effects and underlying mechanisms of gastrodin in the treatment of CNS diseases, and to assess its potential for further development as a lead drug in both biomedicine and traditional Chinese medicine. Studies on the pharmacological effects of gastrodin on the CNS indicate that it may exert anti-neurodegenerative, cerebrovascular protective, and ameliorative effects on diabetic encephalopathy, perioperative neurocognitive dysfunction, epilepsy, Tourette's syndrome, depression and anxiety, and sleep disorders through various mechanisms. To date, 110 gastrodin products have been approved for clinical use, but further multicenter clinical case-control studies are relatively scarce. Preclinical studies have confirmed that gastrodin can be used to treat CNS-related disorders. However, important concerns need to be addressed in the context of likely non-specific, assay interfering effects when gastrodin is studied using in vitro and in silico approaches, calling for a systematic assessment of the evidence to date. High-quality clinical trials should have priority to evaluate the therapeutic safety and clinical efficacy of gastrodin. Further experimental research using appropriate in vivo models is also needed, focusing on neurodegenerative diseases, cerebral ischemic and hypoxic diseases, brain damage caused by methamphetamine or heavy metals, and epilepsy.

The potential therapeutic value of the natural plant compounds matrine and oxymatrine in cardiovascular diseases.

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-ß1/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.

Progress of natural sesquiterpenoids in the treatment of hepatocellular carcinoma.

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, multi-component, 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.

Pharmacological mechanisms of puerarin in the treatment of Parkinson's disease: An overview.

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-3ß/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.

Neolignans in Magnolia officinalis as natural anti-Alzheimer's disease agents: A systematic review.

BACKGROUND: Magnolia officinalis, a traditional herbal medicine widely used in clinical practice, exerts antibacterial, anti-tumor, anti-inflammatory, antioxidant, and anti-aging activities. Neolignans are the main active ingredients of M. officinalis and exert a wide range of pharmacological effects, including anti-Alzheimer's disease (AD) activity. OBJECTIVE: To summarize the published data on the therapeutic effect and mechanism of neolignans on AD in vivo and in vitro. METHODS: PubMed, Web of Science, Google Scholar, and Scopus were systematically reviewed (up to March 1, 2024) for pre-clinical studies. RESULTS: M. officinalis-derived neolignans (honokiol, magnolol, 4-O-methylhonokiol, and obovatol) alleviated behavioral abnormalities, including learning and cognitive impairments, in AD animal models. Mechanistically, neolignans inhibited Aß generation or aggregation, neuroinflammation, and acetylcholinesterase activity; promoted microglial phagocytosis and anti-oxidative stress; alleviated mitochondrial dysfunction and energy metabolism, as well as anti-cholinergic deficiency; and regulated intestinal flora. Furthermore, neolignans may achieve neuroprotection by regulating different molecular pathways, including the NF-κB, ERK, AMPK/mTOR/ULK1, and cAMP/PKA/CREB pathways. CONCLUSIONS: Neolignans exert anti-AD effects through multiple mechanisms and pathways. However, the exact targets, pharmacokinetics, safety, and clinical efficacy in patients with AD need further investigation in multi-center clinical case-control studies.

Resveratrol for inflammatory bowel disease in preclinical studies: a systematic review and meta-analysis.

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-α (TNF-α), 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.

Network Pharmacology and Molecular Docking Validation to Explore the Pharmacological Mechanism of Zhuling Decoction against Nephrotic Syndrome.

BACKGROUND: In recent years, the incidence and prevalence of Nephrotic Syndrome (NS) have been increasing. Zhuling Decoction (ZLD), a classical Chinese medicine, has been clinically proven to be effective for the treatment of NS. However, its underlying mechanism and pharmacodynamic substances remain unclear. OBJECTIVE: This study aimed to explore the mechanism of action and chemical components of ZLD against NS using network pharmacology and molecular docking. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicines (BATMAN-TCM), and SwissTargetPrediction databases were used to screen the principal ingredients and the associated targets of ZLD. NS-related targets were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, Therapeutic Target Database (TTD), and Drugbank databases. Shared targets were derived by the intersection of ZLD- and NS-associated targets. Protein-interaction relationships were analyzed using the STRING database and Cytoscape. A visualized drug-active compound-target network of ZLD was established using Cytoscape. Analyses of gene enrichment were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Molecular docking was performed to assess the binding activity between active components and hub targets. RESULTS: Polyporusterone E, cerevisterol, alisol B, and alisol B 23-acetate were the primary potential ingredients of ZLD. HMGCR, HSD11B1, NOS2, NR3C1, and NR3C2 were the hub targets of ZLD against NS. Molecular docking showed that polyporusterone E, cerevisterol, and alisol B had high binding activities with targets HMGCR, HSD11B1, and NOS2. CONCLUSION: In summary, this study suggests that the main active compounds (polyporusterone E, cerevisterol, alisol B) may have important roles for ZLD acting against NS by binding to hub targets (HMGCR, HSD11B1, and NOS2) and modulating PI3K-Akt, Ras, MAPK, and HIF-1 signaling pathways.

Discovery of novel pyrrolo[2,1-c][1,4]benzodiazepine-3,11-dione (PBD) derivatives as selective HDAC6 inhibitors for the efficient treatment of idiopathic pulmonary fibrosis (IPF) in vitro and in vivo.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by a progressive fibrotic phenotype. Immunohistochemical studies on HDAC6 overexpression in IPF lung tissues confirmed that IPF is associated with aberrant HDAC6 activity. We herein developed a series of novel HDAC6 inhibitors that can be used as potential pharmacological tools for IPF treatment. The best-performing derivative H10 showed good selectivity for multiple isoforms of the HDAC family. The structural analysis and structure-activity relationship studies of H10 will contribute to optimizing the binding mode of the new molecules. The pharmacological mechanism of H10 to inhibit pulmonary fibrosis was validated, and its ability to inhibit the IPF phenotype was also demonstrated. Moreover, H10 showed satisfactory metabolic stability. The efficacy of H10 was also determined in a mouse model of bleomycin-induced pulmonary fibrosis. The results highlighted in this paper may provide a reference for the identification of new drug molecules for the treatment of IPF.

Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence.

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.

A systematic review: Sinomenine.

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.