Medicarpin suppresses lung cancer cell growth in vitro and in vivo by inducing cell apoptosis.

Lung cancer (LC) is the leading cause of cancer deaths worldwide. Surgery, chemoradiotherapy, targeted therapy, and immunotherapy are considered dominant treatment strategies for LC in the clinic. However, drug resistance and meta-stasis are two major challenges in cancer therapies. Medicarpin (MED) is an isoflavone compound isolated from alfalfa, which is usually used in traditional medicine. This study was de sig ned to evaluate the anti-LC effect and reveal the underlying mechanisms of MED in vivo and in vitro. We found that MED could significantly inhibit proliferation, induce apoptosis, and cell cycle arrest of A549 and H157 cell lines. Basically, MED induced cell apoptosis of LC cells by upregu lating the expression of pro-apoptotic proteins BAX and Bak1, leading to the cleavage of caspase-3 (Casp3). Moreover, MED inhibited the proliferation of LC cells via downregulating the expression of proliferative protein Bid. Overall, MED inhibited LC cell growth in vitro and in vivo via suppressing cell proliferation and inducing cell apoptosis, suggesting the therapeutic potential of MED in treating LC.

The effect of green coffee extract supplementation on obesity indices: critical umbrella review of interventional meta-analyses.

Despite a multitude of investigations assessing the impact of green coffee extract supplementation on obesity indices, there is still a great deal of heated debate regarding the benefits of this intervention in obesity management. Therefore, in order to clarify the effect of green coffee extract on waist circumference (WC), body mass index (BMI) and body weight (BW), we conducted an umbrella review of interventional meta-analyses. The Web of Science, Scopus, PubMed/Medline, and Embase databases were searched using specific keywords and word combinations. The umbrella meta-analysis was performed using the Stata software version 17 (Stata Corp. College Station, Texas, USA). We pooled effect sizes (ES) and confidence intervals (CI) for the outcomes using the random effects model (the DerSimonian and Laird method). In total, 5 eligible meta-analyses were included in the final quantitative assessment. Data pooled from 5 eligible papers revealed that green coffee extract can reduce BW (WMD: -1.22 kg, 95% CI: -1.53 to -0.92, p < 0.001), BMI (WMD: -0.48 kg/m2, 95% CI: -0.67 to -0.29, p < 0.001) and WC (WMD: -0.55 cm, 95% CI: -0.80 to -0.31, p < 0.001). Subgroup analyses highlighted that green coffee extract supplementation in dosages ≤600 mg/day and interventions lasting >7 wk are more likely to decrease BW. The present umbrella meta-analysis confirms the beneficial effects of green coffee extract in reducing WC, BMI, and BW. Thus, we may infer that green coffee extract can be used as a complementary therapy in the management of obesity.

A comprehensive review of antitumor properties of Angelica species and their antitumor-responsible constituents and the underlying molecular mechanisms involved in tumor inhibition.

Angelica species have been traditionally used for their medicinal properties. Recent studies have suggested their potential use as anticancer agents, making them an area of interest for further research. The review aims to summarize the current understanding of the potential anticancer effects of Angelica species and to provide insights for further research in this area. We searched for "Angelica" related information on Google Scholar, PubMed, ScienceDirect, Wiley, Science Citation Index Finder, and Springer link by searching keywords such as "Angelica," "Angelica phytochemical," "Angelica antitumor effect," "Angelica molecular mechanisms," and "Angelica clinical application." Included articles focused on the Angelica plant's anticancer properties and clinical studies, while non-cancer-related biological or phytochemical investigations were excluded. We conducted a comprehensive search of books, journals, and databases published between 2001 and 2023, identifying 186 articles for this narrative review. The articles were analyzed for their potential anticancer properties and therapeutic applications. Active compounds in the Angelica genus, such as coumarins, furanocoumarins, phthalides, and polysaccharides, exhibit anticancer properties through various mechanisms. Specific species, like A. archangelica, Angelica sinensis, A. gigas, and A. ksiekie, have the potential as anticancer agents by targeting cellular pathways, generating reactive oxygen species, and inducing apoptotic cell death. Further research into the properties of the Angelica genus is needed for developing new treatments for cancer. Phytochemicals from Angelica species possess potential as anticancer agents, requiring further research for the development of effective, low-cost, and low-toxicity cancer treatments compared to synthetic antitumor drugs.

Assembly of Celastrol to Zeolitic Imidazolate Framework-8 by Coordination as a Novel Drug Delivery Strategy for Cancer Therapy.

Celastrol (Cel), a compound derived from traditional Chinese medicine Tripterygium wilfordii Hook. F, has attracted considerable attention as an anticancer drug. However, its clinical application is limited due to its low bioavailability and potential toxicity. With the advancement of nanoscale metal organic frameworks (MOF), the nano-delivery of drugs can effectively improve those disadvantages. Nevertheless, hydrophobic drugs apparently cannot be encapsulated by the hydrophilic channels of MOF-based drug delivery systems. To address these issues, a new assembly strategy for hydrophobic Cel was developed by coordinating the deprotonated Cel to zeolitic imidazolate framework-8 (ZIF-8) with the assistance of triethylamine (Cel-ZIF-8). This strategy greatly elevates the assembly efficiency of Cel from less than 1% to ca. 80%. The resulted Cel-ZIF-8 remains stable in the physiological condition while dissociating and releasing Cel after a 45-minute incubation in an acidic tumor microenvironment (pH 5.5). Furthermore, Cel-ZIF-8 is proved to be easily taken up by cancer cells and exhibits a better therapeutic effect on tumor cells than free Cel. Overall, the Cel-ZIF-8 provides a novel assembly strategy for hydrophobic drugs, and the findings are envisaged to facilitate the application of Cel in cancer therapies.

Pharmacokinetics of costunolide and dehydrocostuslactone after oral administration of Radix aucklandiae extract in normal and gastric ulcer rats.

Costunolide and dehydrocostuslactone are the main active ingredients of Radix Aucklandiae (RA). An accurate and sensitive LC-MS/MS method was established to simultaneously determine contents of costunolide and dehydrocostuslactone in plasma. There were significant differences in pharmacokinetic parameters (AUC0-t, Cmax,1, Cmax,2, Tmax,1, Vd, and CL) of costunolide and dehydrocostuslactone between RA group and costunolide group or dehydrocostuslactone group. The relative bioavailability of costunolide or dehydrocostuslactone of RA extract was improved. As compared to normal group, the Tmax,2 values of dehydrocostuslactone of RA in gastric ulcer group were prolonged, while the Cmax,1, Cmax,2, and AUC0-t values decreased.

Fimbriatols A-J, Highly Oxidized ent-Kaurane Diterpenoids from Traditional Chinese Plant Flickingeria fimbriata (B1.) Hawkes.

Fimbriatols A-J (1-10), ten new ent-kaurane diterpenoids possessing differently highly oxidized sites, were isolated from Flickingeria fimbriata (B1.) Hawkes. The structures of these new compounds were determined by HRESI-MS, NMR, CD spectra and X-ray diffraction analysis. Compound 1 displayed moderately inhibitory ratio (48.5%) compared with the positive compound NSC-87877 (81.6%) at the concentration of 0.022 µg/mL. Compounds 7-10 possess 3, 4-seco-ent-kaurane skeleton containing a disaccharide moiety with an unusual linkage at C-2' to C-1'' instead of the common linkage at C-6' to C-1'', and this is the first report in 600 more ent-kauranes found in nature, which might be originated from ent-kaurane diterpenoids through post-modified reactions of Baeyer-Villiger oxygenation and glycosylation.

Classification of Mixtures of Chinese Herbal Medicines Based on a Self-organizing Map (SOM).

Chinese Herbal Medicines (CHMs) are typically mixtures of compounds and are often categorized into cold and hot according to the theory of Chinese Medicine. This classification is essential for guiding the clinical application of CHMs. In this study, three types of molecular descriptors were used to build models for classification of 59 CHMs with typical cold/hot properties in the training set taken from the original records on properties in China Pharmacopeia as reference. The accuracy and the Matthews correlation coefficient of the models were validated by a test set containing other 56 CHMs. The best model produced the accuracies of 94.92 % and 83.93 % on training set and test set, respectively. The MACCS fingerprint model is robust in predicting hot/cold properties of the CHMs from their major constituting compounds. This work shows how a classification model for data consisting of multi-components can be developed. The derived model can be used for the application of Chinese herbal medicines.

Metabolic Profile Changes of CCl4-Liver Fibrosis and Inhibitory Effects of Jiaqi Ganxian Granule.

Jiaqi Ganxian Granule (JGG) is a famous traditional Chinese medicine, which has been long used in clinical practice for treating liver fibrosis. However, the mechanism underlying its anti-hepatic fibrosis is still not clear. In this study, an Ultra-Performance Liquid Chromatography-Time-Of-Flight Mass Spectrometry (UPLC-TOF-MS)-based metabolomics strategy was used to profile the metabolic characteristic of serum obtained from a carbon tetrachloride (CCl4)-induced hepatic fibrosis model in Sprague-Dawley (SD) rats with JGG treatment. Through Principal Component Analysis (PCA) and Partial Least Square Discriminant Analysis (PLS-DA), it was shown that metabolic perturbations induced by CCl4 were inhibited after treatment of JGG, for 17 different metabolites related to CCl4. Among these compounds, the change tendency of eight potential drug targets was restored after the intervention with JGG. The current study indicates that JGG has a significant anti-fibrosis effect on CCl4-induced liver fibrosis in rats, which might be by regulating the dysfunction of sphingolipid metabolism, glycerophospholipid metabolism, N-acylethanolamine biosynthesis, fat digestion and absorption, while glycerophospholipid metabolism played vital roles in the inhibitory effects of JGG on hepatic fibrosis according to Metabolic Pathway Analysis (MetPA). Our findings indicated that the metabolomics approach may provide a useful tool for exploring potential biomarkers involved in hepatic fibrosis and elucidate the mechanisms underlying the action of therapies used in traditional Chinese medicine.

A new naphthalenone isolated from the green walnut husks of Juglans mandshurica Maxim.

Phytochemical study of green walnut husks of Juglans mandshurica Maxim. led to the isolation of a new naphthalenone, (4R)-3,4-dihydro-4-butoxy-5-hydroxy-naphthalen-1(2H)-one (1), together with 16 known compounds. Compounds 4-6, 13, 14 and 17 were isolated from the genus Juglans for the first time, and their chemotaxonomic significance was also evaluated.

UPLC-Q/TOF MS standardized Chinese formula Xin-Ke-Shu for the treatment of atherosclerosis in a rabbit model.

Xin-Ke-Shu (XKS), a patent traditional Chinese medicine (TCM) preparation, has been commonly used for the treatment of coronary heart disease in China. In order to understand its mechanism of action, a metabonomic approach based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) was utilized to profile the plasma metabolic fingerprints of atherosclerosis (AS) rabbits with and without XKS treatment. The metabolic profile of model group clearly separated from normal, and that of XKS group was closer to the control group. Metabolites with significant changes during atherosclerosis were characterized as potential biomarkers related to the development of atherosclerosis by using orthogonal partial least-squares-discriminate analysis (OPLS-DA). Twenty potential biomarkers, including l-acetylcarnitine (1), propionylcarnitine (2), unknown (3), phytosphingosine (4), glycoursodeoxycholic acid (5), LPC(14:0) (6), sphinganine (7), LPC(20:5) (8), LPC(16:1) (9), LPC(18:2) (10), LPC(18:3) (11), LPC(22:5) (12), LPC(16:0) (13), LPC(18:1) (14), LPC(22:4) (15), LPC(17:0) (16), LPC(20:2) (17), elaidic carnitine (18), LPC(18:0) (19) and LPC(20:1) (20), were identified by their accurate mass and MS(E) spectra. The derivations of those biomarkers can be regulated by administration of XKS, which suggested that the intervention effect of XKS against AS may involve in regulating the lipid perturbation including fatty acid ß-oxidation pathway, sphingolipid metabolism, glycerophospholipid metabolism and bile acid biosynthesis. This study indicated that the UPLC-Q/TOF MS-based metabonomics not only gave a systematic view of the pathomechanism of AS, but also provided a powerful tool to study the efficacy and mechanism of complex TCM prescriptions.

Chinese herbs and their active ingredients for activating xue (blood) promote the proliferation and differentiation of neural stem cells and mesenchymal stem cells.

Some Chinese herbs are anti-thrombolysis, and anti-inflammatory, improves brain RNA content, promotes brain protein synthesis, enhances dopamine function, regulates brain hormones, and improves microcirculation in central nervous system that might improve, repair and rehabilitation from the stroke and brain injury. Specific Chinese herbs and their components, such as Acanthopanax, Angelica, could maintain the survival of neural stem cells, and Rhodiola, Ganoderma spore Polygala, Tetramethylpyrazine, Gardenia, Astragaloside and Ginsenoside Rg1 promoted proliferation of neural stem cells, and Rhodiola, Astragaloside promoted differentiation of neural stem cell into neuron and glia in vivo. Astragalus, Safflower, Musk, Baicalin, Geniposide, Ginkgolide B, Cili polysaccharide, Salidroside, Astragaloside, Antler polypeptides, Ginsenoside Rg1, Panax notoginseng saponins promoted proliferation and differentiation of neural stem cells in vitro. Salvia, Astragalus, Ginsenoside Rg1, P. notoginseng saponins, Musk polypeptide, Muscone and Ginkgolide B promoted neural-directed differentiation of MSCs into nerve cells. These findings are encouraging further research into the Chinese herbs for developing drugs in treating patients of stroke and brain injury.

Molecular network and chemical fragment-based characteristics of medicinal herbs with cold and hot properties from Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicines (HMs) is one of the great herbal systems of the world, which play an important role in current health care system in many countries. In the view of tradition Chinese medicine (TCM) theory, Yin-yang and five-elements theory is the central theory, which is used to explain how the world and body work. Under the guidance of such philosophy, TCM considers that HMs have different properties, which are the important factors for prescribing herbal formulae; such prescriptions are based on TCM pattern classification in clinical practice. The cold and hot property are commonly defined for HM property identification; however, the biological activities that are related to the HM property remain a mystery because of a lack of appropriate methods. A bioinformatics approach was applied to identify the distinguishing biological activities of HMs that have these cold and hot properties. MATERIAL AND METHODS: Twenty HMs with typical cold and hot properties (10 cold and 10 hot) were selected based on TCM clinical application records and Chinese pharmacopeia. The active target proteins of each HM were searched in the PubChem database and were analyzed in Ingenuity Pathway Analysis (IPA) platform to find out the HM property-related biological activities. In addition, the main compounds of the HMs were fragmented using a fragment-based approach and were analyzed for the purpose of deciphering the properties. RESULTS: The main biological networks of HMs with cold and hot properties include cell cycle, cellular growth, proliferation and development, cancer, cytokine signaling, and intracellular and second messenger signaling; 11 specific pathways are presented to be perturbed only by HMs with the hot property, and the 27 specific target protein molecules include PRKACA, PRKCA, PRKCB, PRKCD, PRKCE, PRKCG, PRKD1, TLR4, TLR7, TLR8, TLR9, HTR4, HTR6, HTR7, HTR2A, HTR1B, HTR2B, GNAO1, GNAI1, TNF, IL8, ROCK2, AKT1, MAPK1, RPS6KA1, RPS6KA3 and JAK2, which are involved in the biological network. One specific pathway is detected to be involved in the biological network of HMs with the cold property, the specific molecules are RAN and KPNB1. Cold propertied HMs show intensive toxicity in the heart, liver and kidney compared with hot HMs, which is likely to be correlated with the specific chemical fragments constructions in the HMs with the cold property, such as long chain alkenes, Benzo heterocycle and azotic heterocycle according to the chemical fragment analysis for the HMs. CONCLUSIONS: Inflammation and immunity regulation are more related to HMs with the hot property, and cold propertied HMs possess the tendency to impact cell growth, proliferation and development. Integrative bioinformatics analysis and chemical structure analysis are a promising methods for identifying the biological activity of HM properties.

Comparative pharmacokinetics of naringin in rat after oral administration of chaihu-shu-gan-san aqueous extract and naringin alone.

Chaihu-Shu-Gan-San (CSGS), a traditional Chinese medicine (TCM) formula containing seven herbal medicines, has been used in the clinical treatment of gastritis, peptic ulcer, irritable bowel syndrome and depression in China. In order to explore the interaction between naringin and other constituents in CSGS, the pharmacokinetic difference of naringin in rats after oral administration of CSGS aqueous extract and naringin alone was investigated. The pharmacokinetic parameters of naringin in rats were achieved by quantification of its aglycone, naringenin by LC-MS/MS method. The double peaks phenomenon was observed in both serum profiles of rats after orally administered CSGS aqueous extract and naringin alone. However, the T1/2b was significantly decreased in rats given CSGS aqueous extract compared with naringin alone, and the mean residence time (MRT) and the area under the serum concentration-time curve (AUC0-τ) were higher than those of naringin, which indicated that naringin in CSGS had higher bioavailability, longer term efficacy and somewhat faster metabolism and excretion than those of naringin. The results suggested that certain ingredients co-exist in CSGS could influence pharmacokinetic behavior of naringin. This also provides a reference for human studies.

Qualitative and quantitative determination of ten iridoids and secoiridoids in Gentiana straminea Maxim. by LC-UV-ESI-MS.

A simple and accurate HPLC-UV/MS method was developed for the simultaneous determination of ten iridoids and secoiridoids in the roots of Gentiana straminea Maxim. Separations were performed on a Kromasil-C18 column by gradient elution using methanol and water containing phosphoric acid. Analytes were identified by HPLC coupled with ESI-MS experiments. The chromatographic method was validated for selectivity, linearity, precision, limit of detection, limit of quantification, accuracy, and stability. The developed assay could be considered as a suitable quality control method for G. straminea and other "Qinjiao" herbs.

Urinary metabonomics study of anti-depressive effect of Chaihu-Shu-Gan-San on an experimental model of depression induced by chronic variable stress in rats.

Chaihu-Shu-Gan-San (CSGS), a traditional Chinese medicine (TCM) formula, has been effectively used for the treatment of depression in clinic. However, studies of its anti-depressive mechanism are challenging, accounted for the complex pathophysiology of depression, and complexity of CSGS with multiple constituents acting on different metabolic pathways. The variations of endogenous metabolites in rat model of depression after administration of CSGS may offer deeper insights into the anti-depressive effect and mechanism of CSGS. In this study, metabonomics based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to profile the metabolic fingerprints of urine obtained from chronic variable stress (CVS)-induced depression model in rats with and without CSGS treatment. Through partial least squares-discriminate analysis, it was observed that metabolic perturbations induced by chronic variable stress were restored in a time-dependent pattern after treatment with CSGS. Metabolites with significant changes induced by CVS, including 3-O-methyldopa (1), pantothenic acid (2), kynurenic acid (3), xanthurenic acid (4), 2,8-dihydroxyquinoline glucuronide (5), 5-hydroxy-6-methoxyindole glucurnoide (8), l-phenylalanyl-l-hydroxyproline (9), indole-3-carboxylic acid (10), proline (11), and the unidentified metabolites (6, 2.11min_m/z 217.0940; 7, 2.11min_m/z 144.0799), were characterized as potential biomarkers involved in the pathogenesis of depression. The derivations of all those biomarkers can be regulated by CSGS treatment except indole-3-carboxylic acid (10), which suggested that the therapeutic effect of CSGS on depression may involve in regulating the dysfunctions of energy metabolism, tryptophan metabolism, bone loss and liver detoxification. This study indicated that the rapid and noninvasive urinary metabonomics approach may be a powerful tool to study the efficacy and mechanism of complex TCM prescriptions.

[Identification method with significant specificity of volatile oil of Pogostemon cablin].

OBJECTIVE: To develop an identification method with significant specificity for patchouli oil. METHOD: The fingerprint was performed by gas chromatography with patchouli alcohol and pogostone as chemical markers. RESULT: The similarity of 12 samples were higher than 0.9 and it can be used to identify the characteristics of patchouli oil. CONCLUSION: The GC fingerprint can be used for identification of patchouli oil.

[Comparative study on two methods of back propagation network test in TCM syndrome typing of depression].

OBJECTIVE: To compare the effect of the two methods of back propagation network (BPN) test on TCM syndrome typing of depression. METHODS: Test was carried out by two methods as following: (1) Cross train-test method: 1731 patients with depression typed to 5 syndrome types were randomly divided into 2 groups, and they were trained and tested in turn; (2) Round-Robin method: Test was conducted in an altered cycle mode, that is, in a cycle, one out of the 1731 patients were selected to be tested, while the others were trained, the next cycle started when the test on the selected patient was finished and another one for test was selected. In this way, one cycle after the other, until all patients had been tested. RESULT: The total training sensitivity of the two methods was 97.9% and 98.2% respectively, and the total testing sensitivity was 72.7% and 74.2% respectively. CONCLUSION: (1) The five TCM syndrome types of depression could be well differentiated by BPN, which is valuable for TCM syndrome typing in certain extent; (2) The sensitivity of Round-Robin method is slightly higher than that of Cross train-test method, but in comparison between them no remarkable significance was shown.