A novel strategy for the multi-components division and discovering pharmacodynamic material basis of Chinese herbal compounds: A case study of Xian-Ling-Gu-Bao capsule.

The therapeutic effects of Chinese herbal compounds are often achieved through the synergistic interactions of multiple ingredients. However, current research predominantly focuses on individual ingredients, neglecting the holistic nature of Chinese herbal compounds. This study proposes a novel strategy to elucidate the pharmacodynamic material basis of Chinese herbal compounds based on their multi-components (components named 'ZuFen' in China, it refers to multiple ingredients with similar chemical structures) composition, using the Xian-Ling-Gu-Bao (XLGB) capsule as a case study. Cheminformatics-based components partitioning was conducted after sourcing ingredients from various databases, resulting in a total of 856 ingredients which were categorized into nine major components. Furthermore, the pharmacodynamic ingredients of XLGB capsule were determined by analyzing the ingredients that were absorbed into the bloodstream. Through a combination of these ingredients and screening for absorption, the Dipsacus asper saponin components, Psoralea corylifolia coumarin components, and Epimedium flavonoid polyglycosides components were isolated. The anti-osteoporosis efficacy of these components were evaluated in zebrafish, demonstrating their capability to reverse mineralization reduction caused by prednisolone. These findings further support the idea that these components serve as the material basis for the pharmacological efficacy of XLGB capsule. This study provides a novel systematic strategy for discovering the pharmacodynamic material basis of the efficacy of Chinese herbal compounds based on a 'multi-components' perspective.

Protective Application of Chinese Herbal Compounds and Formulae in Intestinal Inflammation in Humans and Animals.

Intestinal inflammation is a chronic gastrointestinal disorder with uncertain pathophysiology and causation that has significantly impacted both the physical and mental health of both people and animals. An increasing body of research has demonstrated the critical role of cellular signaling pathways in initiating and managing intestinal inflammation. This review focuses on the interactions of three cellular signaling pathways (TLR4/NF-κB, PI3K-AKT, MAPKs) with immunity and gut microbiota to explain the possible pathogenesis of intestinal inflammation. Traditional medicinal drugs frequently have drawbacks and negative side effects. This paper also summarizes the pharmacological mechanism and application of Chinese herbal compounds (Berberine, Sanguinarine, Astragalus polysaccharide, Curcumin, and Cannabinoids) and formulae (Wumei Wan, Gegen-Qinlian decoction, Banxia xiexin decoction) against intestinal inflammation. We show that the herbal compounds and formulae may influence the interactions among cell signaling pathways, immune function, and gut microbiota in humans and animals, exerting their immunomodulatory capacity and anti-inflammatory and antimicrobial effects. This demonstrates their strong potential to improve gut inflammation. We aim to promote herbal medicine and apply it to multispecies animals to achieve better health.

Successful Treatment of Psoriasis Combined with Bullous Pemphigoid with Dupilumab: A Case Report.

Psoriasis is an immune-mediated chronic inflammatory disease that can be combined with complications such as diabetes, cardiovascular disease, obesity, and kidney disease. The comorbidity of psoriasis with autoimmune bullous diseases (AIBD) has been reported previously in several cases, the most frequent of which is bullous pemphigoid (BP). The underlying mechanisms of psoriasis with BP are not clear and there are no uniform treatment criteria. Based on previous case reports, the coexistence of psoriasis and BP may be related to inflammatory activity, medications, phototherapy, and infection. We report a case of a psoriasis patient who developed BP after taking Chinese herbal compounds and was successfully treated with dupilumab, which is the first reported case of applying dupilumab to treat psoriasis with BP comorbidities.

The traditional Chinese medicine and non-small cell lung cancer: from a gut microbiome perspective.

Non-small cell lung cancer (NSCLC) is one of the most serious diseases affecting human health today, and current research is focusing on gut flora. There is a correlation between intestinal flora imbalance and lung cancer, but the specific mechanism is not clear. Based on the "lung and large intestine being interior-exteriorly related" and the "lung-intestinal axis" theory. Here, based on the theoretical comparisons of Chinese and western medicine, we summarized the regulation of intestinal flora in NSCLC by active ingredients of traditional Chinese medicine and Chinese herbal compounds and their intervention effects, which is conducive to providing new strategies and ideas for clinical prevention and treatment of NSCLC.

Chinese herbal medicine for the treatment of cardiovascular diseases ─ Targeting cardiac ion channels.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality, imposing an increasing global health burden. Cardiac ion channels (voltage-gated NaV, CaV, KVs, and others) synergistically shape the cardiac action potential (AP) and control the heartbeat. Dysfunction of these channels, due to genetic mutations, transcriptional or post-translational modifications, may disturb the AP and lead to arrhythmia, a major risk for CVD patients. Although there are five classes of anti-arrhythmic drugs available, they can have varying levels of efficacies and side effects on patients, possibly due to the complex pathogenesis of arrhythmias. As an alternative treatment option, Chinese herbal remedies have shown promise in regulating cardiac ion channels and providing anti-arrhythmic effects. In this review, we first discuss the role of cardiac ion channels in maintaining normal heart function and the pathogenesis of CVD, then summarize the classification of Chinese herbal compounds, and elaborate detailed mechanisms of their efficacy in regulating cardiac ion channels and in alleviating arrhythmia and CVD. We also address current limitations and opportunities for developing new anti-CVD drugs based on Chinese herbal medicines.

Mechanism of Chinese Herbal Compounds Capable of Invigorating Qi and Activating Blood in Intervention of Hematogenous Metastasis of Malignant Tumors： A Review / 中国实验方剂学杂志

Metastasis is the main cause of poor prognosis of malignant tumors， and intervention with metastasis is the key measure in the treatment of malignant tumors. Hematogenous metastasis， the most common tumor metastasis， falls into the category of "Chuanshe" in traditional Chinese medicine （TCM）， with Qi deficiency and blood stasis as the critical pathogenesis. In the fight against malignant tumors， TCM emphasizes the reinforcement of healthy Qi and the elimination of pathogenic factors， exhibiting its action advantages of multiple targets， multiple mechanisms， and multiple levels. Extensive clinical evidence has shown the exact efficacy of Chinese herbal compounds designed for invigorating Qi and activating blood in delaying the progression of tumor disease and prolonging the survival period of patients. In view of the important role of hematogenous metastasis in the prognosis of tumors， more and more studies have explored the effects and mechanisms of Chinese herbal compounds capable of invigorating Qi and activating blood in intervening in hematogenous metastasis. This paper summarized the relevant literature reports in China and abroad on the intervention of Chinese herbal compounds capable of invigorating Qi and activating blood in the hematogenous metastasis of malignant tumors， in order to provide a theoretical basis for the clinical application of Qi-invigorating and blood-activating therapy in the treatment of malignant tumors. It has been found that Chinese herbal compounds formulated for invigorating qi and activating blood are effective in hindering several key steps in hematogenous metastasis through various mechanisms， including regulating the expression of cell adhesion molecules， inhibiting extracellular matrix degradation and angiogenesis， enhancing the killing effect of immunity， and improving blood hypercoagulability and hyperviscosity. Furthermore， the combination of invigorating Qi and activating blood targets the pathogenesis essence （Qi deficiency and blood stasis， characterized by sthenia in origin and asthenia in superficiality） of malignant tumor much better. Some comparative studies have demonstrated that the anti-metastasis effect of Qi-invigorating and blood-activating therapy is significantly stronger than that of the Qi-invigorating or blood-activating therapy alone， and such combination avoids the possible risk of the metastasis of malignant tumors triggered by the use of either of them. This study has provided some reference for the current clinical application of TCM for improving the prognosis of malignant tumors.

Efficacy and potential mechanisms of Chinese herbal compounds in coronavirus disease 2019: advances of laboratory and clinical studies.

The Coronavirus disease 2019 (COVID-19) pandemic is still spread and has made a severe public health threat around the world. To improve disease progression, emerging Chinese herbal compounds were used in clinical practice and some agents have proven beneficial in treating COVID-19. Here, the relevant literature from basic researches to clinical application were identified and comprehensively assessed. A variety of Chinese herbal compounds have been reported to be effective in improving symptoms and outcomes in patients with COVID-19, particularly together with routine treatment strategy. The pharmacological activities were mainly attributed to the relief of clinical symptoms, inhibition of cytokine storm, and improvement of organ function. Besides, the development of novel antiviral drugs from medicinal herbs were further discussed. The updated laboratory and clinical studies provided the evidence of Chinese herbal compounds such as Lianhua Qingwen prescription, Shufeng Jiedu prescription, and Qingfei Paidu Tang for the relief of COVID-19. However, both of the randomized controlled trials and real world researches need to be done for supporting the evidence including the efficacy and safety in fighting COVID-19.

Synergistic Effect and Mechanism of Plumbagin with Gentamicin Against Carbapenem-Resistant Klebsiella pneumoniae.

BACKGROUND: Aminoglycosides are one of a few susceptible antimicrobials available for carbapenem-resistant Enterobacteriaceae (CRE). However, the altered pharmacokinetics and increasing drug resistance of aminoglycosides will make them hardly effective if used in monotherapy. The purpose of this study was to identify herbal compounds that potentiate the antibacterial effect of gentamicin against carbapenem-resistant Klebsiella pneumoniae (CRKp) with gentamicin resistance and explore the action mechanisms. METHODS: A collection of 280 Chinese herbal compounds was screened for synergistic effect with gentamicin against CRKp by broth microdilution method according to the standard of the Clinical and Laboratory Standards Institute (CLSI). Intracellular gentamicin was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The membrane potential was evaluated by BacLightTM Bacterial Membrane Potential Kit. Plumbagin-induced metabolite changes of vital metabolic pathways were measured by an optimized untargeted metabolomics method based on gas chromatography-mass spectrometer (GC/MS). Intracellular nicotinamide adenine dinucleotide (NADH) was detected via EnzyChrom NAD/NADH assay kit. RESULTS: We identified plumbagin to remarkably potentiate the antimicrobial activity of gentamicin against the CRKp with gentamicin resistance. Plumbagin at 100 µM could bring the MIC of gentamicin from >16 µg/mL to ~4 µg/mL despite its minimal inhibitory effect on the CRKp. A similar synergistic effect with gentamicin was also observed in an antibiotics-susceptible strain of Klebsiella pneumoniae. Compared with gentamicin monotreatment, the combination group showed a higher intracellular concentration of gentamicin and increased membrane potential in CRKp. Metabolomics analysis indicated remarkable increases of malate and α-ketoglutarate in the tricarboxylic acid (TCA) cycle in the CRKp upon plumbagin treatment. Further analysis revealed higher intracellular NADH concentration in plumbagin-treated CRKp, supporting increased proton-motive force (PMF) that facilitates aminoglycosides uptake. CONCLUSION: Herbal compound plumbagin was identified to stimulate gentamicin uptake by CRKp via enhancing TCA efflux and PMF to achieve a synergistic antibacterial effect. Plumbagin may be used in combination with aminoglycosides for severe CRKp infection by potentiating their therapeutic efficacy and lowering dosage.

Research Progress in the Treatment of Idiopathic Membranous Nephropathy using Traditional Chinese Medicine.

This article reviews the most significant literature of the recent years on the treatment of idiopathic membranous nephropathy (IMN) with traditional Chinese medicine (TCM). One major goal of the article is to classify and summarize the research on the clinical aspects and the associated mechanisms of the use of Chinese herbal compounds and single drugs to treat IMN. It was found that TCM treats IMN via two major approaches: by benefiting qi, activating blood circulation and eliminating dampness, or by benefiting qi and nourishing yin. The method of benefiting qi, to activate blood circulation and eliminate dampness for dredging channels, is the most popular. The commonly used drugs in this approach include Huang Qi (astragalus), Dang Shen (codonopsis root), Bai Zhu (white atractylodes rhizome), Fu Ling (poria cocos), Dang Gui (angelica sinensis), and so on. Several randomized, controlled, clinical trials are reviewed in the article, including a multicenter one.

Prediction Methods of Herbal Compounds in Chinese Medicinal Herbs.

Chinese herbal medicine has recently gained worldwide attention. The curative mechanism of Chinese herbal medicine is compared with that of western medicine at the molecular level. The treatment mechanism of most Chinese herbal medicines is still not clear. How do we integrate Chinese herbal medicine compounds with modern medicine? Chinese herbal medicine drug-like prediction method is particularly important. A growing number of Chinese herbal source compounds are now widely used as drug-like compound candidates. An important way for pharmaceutical companies to develop drugs is to discover potentially active compounds from related herbs in Chinese herbs. The methods for predicting the drug-like properties of Chinese herbal compounds include the virtual screening method, pharmacophore model method and machine learning method. In this paper, we focus on the prediction methods for the medicinal properties of Chinese herbal medicines. We analyze the advantages and disadvantages of the above three methods, and then introduce the specific steps of the virtual screening method. Finally, we present the prospect of the joint application of various methods.

Subchronic toxicity of herbal compound "Jiedu Huayu" granules in rats.

BACKGROUND: "Jiedu Huayu" (JDHY) granules are traditional Chinese herbal compounds that have been used to treat severe liver injury for many years. The purpose of the current study is to evaluate the safety of JDHY granules. METHODS: Subchronic toxicity was tested in male and female rats that were orally administered three different doses (80, 100, and 130 g/kg/d) of JDHY for 13 weeks. Clinical signs, bodyweight, food consumption, hematological and biochemical parameters, organ coefficients, and histological changes were observed during the study. RESULTS: There were no significant changes in toxicity observed in either sex at any dose of JDHY granules treatment. CONCLUSIONS: These results suggest that repeated oral administration of JDHY granules at dosage levels of ≤130 g/kg/d can be considered safe.

Effects of Chinese Herbal Compounds on Levels of Blood Glucose, Froctosamine and Insulin of Diabetic Rats / 中国中医药信息杂志

Objective To observe the effects of Chinese herbal compounds (alkaloid of Coptidis Rhizoma 40%, total saponin of panax notoginseng 35%, and polysaccharide of Ophiopogonis Radix 25%) on levels of blood glucose, fructosamine, and insulin of diabetic rats, and explore mechanism of action.Methods Ten rats were randomly chosen as blank control group, and other rats were used to establish diabetic rat models by STZ intraperitoneal injection. Successfully molding rats were randomly divided into Chinese herbal compounds high, medium, low dose groups, metformin group, and model group, 10 rats in each group. Each rat received gavage for continuous 4 weeks. Then rat blood was collected by cutting head and taking caudal vein. FBG was detected by glucose oxidase method;insulin level was detected by radio-immunity double antibody method;fructosamine content was detected by fructosamine method.Results Compared with the blank control group, model group the levels of FBG, froctosamine content increased, while fasting insulin level were lower after 4 weeks'medication. Compared with the model group, the levels of FBG, froctosamine content in Chinese herbal compounds high and medium dose groups and metformin group were lower, while fasting insulin level increased after 4 weeks'medication (P<0.05).Conclusion TCM herbal compounds can increased the basic insulin level by decreasing the contents of FBG and fructosamine.