(-)-Syringaresinol attenuates ulcerative colitis by improving intestinal epithelial barrier function and inhibiting inflammatory responses.

BACKGROUND: (-)-Syringaresinol (SYR), a natural lignan with significant antioxidant and anti-inflammatory activities, possesses various pharmacological benefits including cardio-protective, antibacterial, anticancer, and anti-aging effects. It was shown that the effectiveness of (+)-syringaresinol diglucoside on the ulcerative colitis (UC) was attributed to the active metabolite (+)-syringaresinol (the enantiomor of SYR). However, the efficacy of SYR against UC remains unclear, and the associated molecular mechanism has not been revealed yet PURPOSE: This study aimed to assess the protective effect of SYR in UC and its underlying mechanism STUDY DESIGN AND METHODS: We examined SYR's protective impact on the intestinal epithelial barrier and its ability to inhibit inflammatory responses in both a lipopolysaccharide (LPS)-induced Caco-2 cell model and a dextran sodium sulfate (DSS)-induced UC mouse model. We also explored the potential signaling pathways regulated by SYR using transcriptome analysis and western blot assay RESULTS: In Caco-2 cells, SYR significantly increased trans-epithelial electrical resistance, reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ), and cyclooxygenase-2 (COX-2) levels, and enhanced cellular tight junction protein expression and distribution. In mice with UC, oral treatment with SYR (10, 20, 40 mg·kg-1) dose-dependently increased body weight, colon length, and expression of tight junction proteins, decreased disease activity index score, spleen coefficient, cytokine serum levels, bacterial translocation, and intestinal damage, and also preserved the ultrastructure of colonic mucosal cells. Transcriptomics indicated that the anti-UC effect of SYR is mediated via the PI3K-Akt/MAPK/Wnt signaling pathway. CONCLUSION: In summary, SYR effectively mitigated the development of UC by enhancing the intestinal epithelial barrier function and attenuating the inflammatory response. The plant-derived product SYR might be a potentially effective therapeutical agent against UC.

Study on the Comprehensive Phytochemicals and the Anti-Ulcerative Colitis Effect of Saussurea pulchella.

BACKGROUND: Saussurea pulchella (SP) is a traditional medicinal plant that is widely used in folk medicine because of its diverse biological activities, particularly its anti-inflammatory effects. However, the alleviation effect of SP on ulcerative colitis (UC) has not yet been realized. PURPOSE: To investigate the chemical composition and therapeutic effect of SP extract against UC. METHODS: First, qualitative and quantitative analysis of SP 75% ethanol extract was performed by UPLC-Q/TOF-MS. Second, a dextran sodium sulfate (DSS) model of UC mice was developed to study the effects of SP on the symptoms, inflammatory factors, oxidative stress indexes and colon histopathology. Third, an integration of network pharmacology with metabolomics was performed to investigate the key metabolites, biological targets and metabolisms closely related to the effect of SP. RESULTS: From the SP ethanol extract, 149 compounds were identified qualitatively and 20 were determined quantitatively. The SP could dose-dependently decrease the DAI score, spleen coefficient and the levels of TNF-α, IL-6, iNOS, MPO and MDA; increase the colon length, GSH level and SOD activity; and protect the intestinal barrier in the UC mice. Moreover, 10 metabolite biomarkers,18 targets and 5 metabolisms were found to play crucial roles in the treatment of UC with SP. CONCLUSIONS: SP 75% ethanol extract could effectively alleviate the progression of UC and, therefore, could be classified as a novel natural treatment for UC.

Neuroprotective Effects and Metabolomics Study of Protopanaxatriol (PPT) on Cerebral Ischemia/Reperfusion Injury In Vitro and In Vivo.

Stroke, one of the leading causes of disability and death worldwide, is a severe neurological disease that threatens human life. Protopanaxatriol (PPT), panaxatriol-type saponin aglycone, is a rare saponin that exists in Panax ginseng and Panax Noto-ginseng. In this study, we established an oxygen-glucose deprivation (OGD)-PC12 cell model and middle cerebral artery occlusion/reperfusion (MCAO/R) model to evaluate the neuroprotective effects of PPT in vitro and in vivo. In addition, metabolomics analysis was performed on rat plasma and brain tissue samples to find relevant biomarkers and metabolic pathways. The results showed that PPT could significantly regulate the levels of LDH, MDA, SOD, TNF-α and IL-6 factors in OGD-PC12 cells in vitro. PPT can reduce the neurological deficit score and infarct volume of brain tissue in rats, restore the integrity of the blood-brain barrier, reduce pathological damage, and regulate TNF-α, IL-1ß, IL-6, MDA, and SOD factors. In addition, the results of metabolomics found that PPT can regulate 19 biomarkers involving five metabolic pathways, including amino acid metabolism, arachidonic acid metabolism, sphingolipid metabolism, and glycerophospholipid metabolism. Thus, it could be inferred that PPT might serve as a novel natural agent for MCAO/R treatment.

Effects of dietary wild bitter melon (Momordica charantia var. abbreviate Ser.) extract on glucose and lipid metabolism in HFD/STZ-induced type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Plant-based extracts to interfere with the onset of diabetes may be a promising approach towards type 2 diabetes mellitus (T2DM). Bitter gourd (Momordica charantia L.) is popularly consumed as an edible and medicinal resource with hypoglycemic effect in China. Wild bitter gourd (Momordica Charantia var. abbreviata Ser.) is a variant of bitter gourd, but there are relatively few studies on it. AIM OF THE STUDY: The purpose of the experiment is to first screen out the most effective extraction part of Momordica charantia L. and Momordica Charantia var. abbreviata Ser. through the hypoglycemic activity experiment in vitro, and by using a high-fat and high-sugar diet with STZ-induced diabetic rat model in vivo to explore the possible mechanism of action against diabetes. MATERIALS AND METHODS: This study first performed α-glucosidase, PTP1B and lipase activities inhibition experiments on the alcohol and water extracts of Momordica charantia L. and Momordica Charantia var. abbreviata Ser. Sprague Dawley rats were either given normal feed or a high sugar and fat diet for four weeks, followed STZ (25 mg/kg, via i. p.) was given. Rats with fasting blood glucose ≥11.1 mmol/l after one week were deemed to be diabetic, treatments were administered for four weeks, and then blood samples were used to evaluate hematological and biochemical indicators, and liver was removed for post-analysis. The expression levels of p-AMPK, AMPK, p-PI3K, PI3K, p-AKT, AKT, p-GSK3ß, GSK3ß, p-IRS-1, IRS-1, GLUT2 were determined by Western blot. At the same time, the chemical components was identified by liquid-mass spectrometry. RESULTS: Data showed that the ethanol extract of wild bitter gourd (WBGE) had the best ability to regulate glucose and lipid metabolism in vitro. Therefore, we further investigated the antidiabetic effects of oral consumption of WBGE on high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in SD rats. WBGE effectively reduced blood glucose and lipid levels, alleviated glucose intolerance and insulin resistant. Moreover, WBGE consumption could also inhibited oxidant responses and inflammatory damage. Mechanism studies have shown that WBGE may act by regulating AMPK/PI3K signaling pathway. On the other hand, the content of total phenol, total flavonoids, total saponins and total polysaccharide were measured by UV, 27 compounds were identified by LC-MS. CONCLUSIONS: These studies explored the role and mechanism of WBGE in regulating glucose and lipid metabolism, and may support the utilization and further investigation of wild bitter gourd as a dietary intervention strategy to prevent diabetes and related metabolic abnormalities.

A Qualitative Analysis of Cultured Adventitious Ginseng Root's Chemical Composition and Immunomodulatory Effects.

The cultivation of ginseng in fields is time-consuming and labor-intensive. Thus, culturing adventitious ginseng root in vitro constitutes an effective approach to accumulating ginsenosides. In this study, we employed UPLC-QTOF-MS to analyze the composition of the cultured adventitious root (cAR) of ginseng, identifying 60 chemical ingredients. We also investigated the immunomodulatory effect of cAR extract using various mouse models. The results demonstrated that the cAR extract showed significant activity in enhancing the immune response in mice. The mechanism underlying the immunomodulatory effect of cAR was analyzed through network pharmacology analysis, revealing potential 'key protein targets', namely TNF, AKT1, IL-6, VEGFA, and IL-1ß, affected by potential 'key components', namely the ginsenosides PPT, F1, Rh2, CK, and 20(S)-Rg3. The signaling pathways PI3K-Akt, AGE-RAGE, and MAPK may play a vital role in this process.

Protective Effects of Protopanaxatriol Saponins on Ulcerative Colitis in Mouse Based on UPLC-Q/TOF-MS Serum and Colon Metabolomics.

Ulcerative colitis (UC) is a chronic, nonspecific inflammation of the bowel that mainly affects the mucosa and submucosa of the rectum and colon. Ginsenosides are the main active ingredients in ginseng and show many therapeutic effects in anti-inflammatory diseases, cancer, and nervous system regulation. Protopanaxatriol saponin (PTS) is an important part of saponins, and there is no research on its pharmacological effects on colitis. In this study, a model of ulcerative colitis in mice was induced by having mice freely drink 3.5% dextran sodium sulfate (DSS) solution, and UPLC-Q-TOF-MS-based metabolomics methods were applied to explore the therapeutic effect and protective mechanism of PTS for treating UC. The results showed that PTS could significantly prevent colon shortening and pathological damage and alleviate abnormal changes in UC mouse physiological and biochemical parameters. Moreover, PTS intervention regulated proinflammatory cytokines such as TNF-α, IL-6, and IL-1 in serum, and MPO and NO in colon. Interestingly, PTS could significantly inhibit UC mouse metabolic dysfunction by reversing abnormal changes in 29 metabolites and regulating eleven metabolic pathways. PTS has potential application in the treatment of UC and could alleviate UC in mice by affecting riboflavin metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, retinol metabolism, and steroid hormone biosynthesis and by regulating pentose and glucuronate conversion, linoleic acid metabolism, phenylalanine metabolism, ether lipid metabolism, sphingolipid metabolism, and tyrosine metabolism, which points at a direction for further research and for the development of PTS as a novel natural agent.

Integrated Metabolomics and Network Pharmacology to Decipher the Latent Mechanisms of Protopanaxatriol against Acetic Acid-Induced Gastric Ulcer.

Gastric ulcer (GU) is a peptic disease with high morbidity and mortality rates affecting approximately 4% of the population throughout the world. Current therapies for GU are limited by the high relapse incidence and side effects. Therefore, novel effective antiulcer drugs are urgently needed. Ginsenosides have shown good anti-GU effects, and the major intestinal bacterial metabolite of ginsenosides, protopanaxatriol (PPT), is believed to be the active component. In this study, we evaluated the anti-GU effect of PPT in rats in an acetic acid-induced GU model. High (H-PPT) and medium (M-PPT) doses of PPT (20.0 and 10.0 mg/mg/day) significantly reduced the ulcer area and the ET-1, IL-6, EGF, SOD, MDA and TNF-α levels in serum were regulated by PPT in a dose-dependent manner. We also investigated the mechanisms of anti-GU activity of PPT based on metabolomics coupled with network pharmacology strategy. The result was that 16 biomarkers, 3 targets and 3 metabolomic pathways were identified as playing a vital role in the treatment of GU with PPT and were further validated by molecular docking. In this study, we have demonstrated that the integrated analysis of metabolomics and network pharmacology is an effective strategy for deciphering the complicated mechanisms of natural compounds.

Correction: UPLC-MS/MS determination and pharmacokinetic study of 26-OH-panaxadiol in rat plasma.

Correction for 'UPLC-MS/MS determination and pharmacokinetic study of 26-OH-panaxadiol in rat plasma' by Meiyu Lin et al., Anal. Methods, 2013, 5, 6656-6662, https://doi.org/10.1039/C3AY41320A.

Role of Ginseng, Quercetin, and Tea in Enhancing Chemotherapeutic Efficacy of Colorectal Cancer.

As the most common gastrointestinal malignancy, colorectal cancer (CRC) remains a leading cause of cancer death worldwide. Although multimodal chemotherapy has effectively improved the prognosis of patients with CRC in recent years, severe chemotherapy-associated side effects and chemoresistance still greatly impair efficacy and limit its clinical application. In response to these challenges, an increasing number of traditional Chinese medicines have been used as synergistic agents for CRC administration. In particular, ginseng, quercetin, and tea, three common dietary supplements, have been shown to possess the potent capacity of enhancing the sensitivity of various chemotherapy drugs and reducing their side effects. Ginseng, also named "the king of herbs", contains a great variety of anti-cancer compounds, among which ginsenosides are the most abundant and major research objects of various anti-tumor studies. Quercetin is a flavonoid and has been detected in multiple common foods, which possesses a wide range of pharmacological properties, especially with stronger anti-cancer and anti-inflammatory effects. As one of the most consumed beverages, tea has become particularly prevalent in both West and East in recent years. Tea and its major extracts, such as catechins and various constituents, were capable of significantly improving life quality and exerting anti-cancer effects both in vivo and in vitro. In this review, we mainly focused on the adjunctive effects of the three herbs and their constituents on the chemotherapy process of CRC.

Protective effect of total Saponins from American ginseng against cigarette smoke-induced COPD in mice based on integrated metabolomics and network pharmacology.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease. Aiming at assessing the effect of total saponins from American ginseng on COPD, both the chemical composition and anti-COPD activity of total saponins from wild-simulated American ginseng (TSW) and field-grown American ginseng (TSF) were investigated in this study. Firstly, a HPLC-ELSD chromatographic method was established to simultaneously determine the contents of 22 saponins in TSW and TSF. Secondly, CS-induced COPD mouse model was established to evaluate the activity of TSW and TSF. The results indicated that both TSW and TSF had the protective effect against COPD by alleviating oxidative stress and inflammatory response. TSW showed a stronger effect than TSF. Thirdly, an integrated approach involving metabolomics and network pharmacology was used to construct the "biomarker-reaction-enzyme-target" correlation network aiming at further exploring the observed effects. As the results, 15 biomarkers, 9 targets and 5 pathways were identified to play vital roles in the treatment of TSW and TSF on COPD. Fourthly, based on network pharmacology and the CS-stimulated A549 cell model, ginsenoside Rgl, Rc, oleanolic acid, notoginsenoside R1, Fe, silphioside B were certified to be the material basis for the stronger effect of TSW than TSF. Finally, the molecular docking were performed to visualize the binding modes. Our findings suggested that both TSW and TSF could effectively ameliorate the progression of COPD and might be used for the treatment of COPD.

Protective Effect of Ethyl Rosmarinate against Ulcerative Colitis in Mice Based on Untargeted Metabolomics.

Aiming at assessing the therapeutic effect of ethyl rosmarinate (ER) on ulcerative colitis (UC), the following activities were performed in vitro and in vivo in the present study. Firstly, a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was established to determine the level of inflammatory factors. Then, a UC mice model induced by dextran sodium sulfate (DSS) was established to further investigate the effects of ER on symptoms, inflammatory factors and colon histopathology. Finally, serum and colon metabolomics studies were performed to identify the biomarkers and metabolisms closely related to the protective effect of ER on UC. The results showed that after ER intervention, the levels of inflammatory factors (NO, TNF-α, IL-1ß and IL-6) and key enzyme (MPO) in cell supernatant, serum or colon were significantly decreased, and the disease activity index and colon tissue damage in mice were also effectively improved or restored. In addition, 28 biomarkers and 6 metabolisms were found to be re-regulated by ER in the UC model mice. Therefore, it could be concluded that ER could effectively ameliorate the progression of UC and could be used as a new natural agent for the treatment of UC.

Comprehensive phytochemicals analysis and anti-myocardial ischemia activity of total saponins of American ginseng berry.

American ginseng berry (AGB) is a new medicinal source. Total saponins of American ginseng berry (TSAGB) are the main active ingredients. The effects and active saponins of TSAGB on myocardial ischemia (MI) rats were evaluated for the first time. First, there were 69 saponins identified or tentatively characterized by Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS/MS) combined with UNIFI platform, among which, about 28 saponins were first identified in AGB. Second, MI model was established by ligating left coronary artery. It has been demonstrated that TSAGB could prevent the ST-segment elevation, reduce myocardial infarct size and levels of aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), and elevate the superoxide dismutase (SOD) level. Finally, network pharmacology combined with molecular docking to screen out four active saponins (ginsenoside Re, Rb3 , Rg3 , and PF11 ) and five key targets (SOD1, LDHA, CKB, GOT2, and ROS1) closely related to MI. PRACTICAL APPLICATIONS: This study enriches the chemical composition of TSAGB, and provides a basis for clarifying the pharmacological substances for anti-myocardial ischemia. TSAGB might be a potential anti-myocardial ischemia agent. The effect might be related to alleviating oxidative stress.

Comprehensive investigation on metabolites of Panax quinquefolium L. in two main producing areas of China based on ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

Jilin Province and Shandong Province are two main American ginseng (AG) producing areas in China. The geographical difference existed in these two provinces. Aiming at evaluating the similarities and differences of the secondary metabolites, the comprehensive metabolite profiling of AG from Jilin Province (AGJ ) and Shandong Province (AGS ) was performed based on UPLC-QTOF-MS for the first time. In screening analysis, a total of 111 shared compounds, with ginsenosides being major components, were identified or tentatively characterized, which indicated that AGJ and AGS were all rich in phytochemicals and contained similar structural types. Untargeted metabolomics analysis indicated that there were significant differences in the contents of certain constituents in AGJ and AGS . Nineteen (12 for AGJ , 7 for AGS ) potential producing area-dependent chemical markers were discovered. Based on the contents and MS responses, ginsenoside Rg1 , Re, and pseudoginsenoside F11 could be considered as the characteristical markers of AGJ , whereas ginsenoside Rg3 and Rh2 of AGS . This comprehensive phytochemical profile study could provide valuable chemical evidence for evaluating the characteristics qualities of AG from various producing areas.

Comprehensive phytochemical profiling of American ginseng in Jilin province of China based on ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry.

American ginseng (AG), the underground part of Panax quinquefolium L., is composed of four morphological regions, including main root (MR), lateral root (LR), fibrous root (FR), and rhizome (RH). In the clinical, MR is the main medicinal region, other regions are rarely attention. Aiming at revealing the chemical composition of AG and making better use of AG, screening analysis and metabolomic analysis were both performed to profile MR, LR, FR, and RH. First, in the systematical screening analysis, a total of 134 compounds (including 122 shared components) with various structural patterns were identified and tentatively characterized. The results indicated that the phytochemicals with various structural types were rich in MR, LR, FR, and RH. Second, 6, 4, 8, and 11 chemical markers were identified from MR, LR, FR, and RH, respectively. Seven triterpene saponins (protopanaxatriol, quinquenoside R1 , ginsenoside Rc, Rk1 , Rg1 , Re, and vinaginsenoside R1 ) might be used for rapid differentiation of four morphological regions. This comprehensive profile study of metabolites illustrated the similarities and differences of phytochemicals in four morphological regions of AG. The results could be used for the quality control of AG and furnish a basis for the further development and utilization of AG sources.

Protopanaxadiol and Protopanaxatriol Ginsenosides Can Protect Against Aconitine-induced Injury in H9c2 Cells by Maintaining Calcium Homeostasis and Activating the AKT Pathway.

ABSTRACT: This study aimed to investigate the effects of protopanaxadiol and protopanaxatriol ginsenosides on aconitine-induced cardiomyocyte injury and their regulatory mechanisms. The effects of ginsenosides on aconitine-induced cardiomyocyte damage were initially evaluated using H9c2 cells, and the molecular mechanisms were elucidated using molecular docking and western blotting. The changes in enzyme content, reactive oxygen species (ROS), calcium (Ca2+) concentration, and apoptosis were determined. Furthermore, an aconitine-induced cardiac injury rat model was established, the cardiac injury and serum physiological and biochemical indexes were measured, and the effects of ginsenoside were observed. The results showed that ginsenoside Rb1 significantly increased aconitine-induced cell viability, and its binding conformation with protein kinase B (AKT) protein was the most significant. In vitro and in vivo, Rb1 protects cardiomyocytes from aconitine-induced injury by regulating oxidative stress levels and maintaining Ca2+ concentration homeostasis. Moreover, Rb1 activated the PI3K/AKT pathway, downregulated Cleaved caspase-3 and Bax, and upregulated Bcl-2 expression. In conclusion, Rb1 protected H9c2 cells from aconitine-induced injury by maintaining Ca2+ homeostasis and activating the PI3K/AKT pathway to induce a cascade response of downstream proteins, thereby protecting cardiomyocytes from damage. These results suggested that ginsenoside Rb1 may be a potential cardiac protective drug.

Synthesis and Anti-Hepatocarcinoma Effect of Amino Acid Derivatives of Pyxinol and Ocotillol.

Aiming at seeking an effective anti-hepatocarcinoma drug with low toxicity, a total of 24 amino acid derivatives (20 new along with 4 known derivatives) of two active ocotillol-type sapogenins (pyxinol and ocotillol) were synthesized. Both in vitro and in vivo anti-hepatocarcinoma effects of derivatives were evaluated. At first, the HepG2 human cancer cell was employed to evaluate the anti-cancer activity. Most of the derivatives showed obvious enhanced activity compared with pyxinol or ocotillol. Among them, compound 2e displayed the most excellent activity with an IC50 value of 11.26 ± 0.43 µM. Next, H22 hepatoma-bearing mice were used to further evaluate the anti-liver cancer activity of compound 2e. It was revealed that the growth of H22 transplanted tumor was significantly inhibited when treated with compound 2e or compound 2e combined with cyclophosphamide (CTX) (p < 0.05, p < 0.01), and the inhibition rates of tumor growth were 35.32% and 55.30%, respectively. More importantly, compound 2e caused limited damage to liver and kidney in contrast with CTX causing significant toxicity. Finally, the latent mechanism of compound 2e was explored by serum and liver metabolomics based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) technology. A total of 21 potential metabolites involved in 8 pathways were identified. These results suggest that compound 2e is a promising agent for anti-hepato-carcinoma, and that it also could be used in combination with CTX to increase efficiency and to reduce toxicity.

Comprehensive phytochemical analysis and sedative-hypnotic activity of two Acanthopanax species leaves.

Acanthopanax senticosus leaves (SCL) and Acanthopanax sessiliflorus leaves (SFL), which are usually made into functional teas, possess similar pharmacological activities. With the aim of revealing their chemical compositions and evaluating their sedative-hypnotic effects, comprehensive metabolite profiling analysis based on ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) and high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) as well as bioassay studies in mice were performed for the first time. Firstly, a total of 75 compounds (including 69 shared components) were identified or briefly characterized. Results indicated that the leaves of the two species were both rich in phytochemicals and contained similar structural types. Secondly, 20 and 7 chemical markers were identified from SCL and SFL, respectively. Five oleanane-type triterpene saponins (ciwujianoside C1, C3, D2, E and saniculoside N) and two lupine-type triterpene saponins (1-deoxychiisanoside and 24-hydroxychiisanoside) may be used for rapid identification of SCL and SFL. Thirdly, the contents of rutin, hederacoside D, ciwujianoside B, -C3, -E and ursolic acid in SCL (0.308%, 0.024%, 0.042%, 0.131%, 0.038%, and 0.255%, respectively) were higher than in SFL (0.067%, 0.005%, 0.012%, 0.015%, 0.002%, and 0.087%, respectively). Fourthly, an in vivo bioassay verified that both SCL and SFL could inhibit autonomous activity, shorten sleep latency and prolong sleep duration in a dose-dependent manner. To a certain degree, SCL showed a higher and more stable effect. The hypnotic effect could be inhibited by flumazenil (FLU). The two leaves not only had an obvious antagonism action of p-chlorophenoxyacetic acid (pCPA) but also showed a synergistic hypnotic effect with 5-hydroxytryptophan (5-HTP). The beneficial bioactivity may be mediated by 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA). Finally, network pharmacology analysis showed that the undifferentiated and differentiated compounds were the material basis for the similar and the different activities of two leaves. Some typical chemical markers (such as saniculoside N, hederacoside D, ciwujianoside C3, -E and ursolic acid, 24-hydroxychiisanoside and 1-deoxyisochiisanoside) were the potential active compounds and could be used as quality markers in the future. The present study furnished a basis for the further development and utilization of the leaves of these two Acanthopanax species.

Design, synthesis and biological evaluation of novel pyxinol derivatives with anti-heart failure activity.

Heart failure (HF) is an important and leading cause of substantial morbidity and mortality globally. The angiotensin-converting enzymatic (ACE) is the causative source for congestive heart failure. Natural products and its derivatives play a vital role in drug discovery and development owing to their efficacy and low toxicity. Pyxinol is a potent natural agent for cardiovascular disease. Thus we investigated the effect on ACE and HF of pyxinol derivatives. We designed and synthesized 32 novel fatty acid ester derivatives of pyxinol via esterification. Among them, compounds 2e (IC50=105 nM) and 3b (IC50=114 nM) displayed excellent ACE inhibitory activity in vitro, and exhibited non-toxic to H9c2 cells. The interactions between ACE and compounds were predicted by molecular docking respectively. In verapamil-induced zebrafish HF model, the activity assay showed that these two derivatives could improve cardiovascular physiological indexes including heart beats, venous congestion, heart dilation, cardiac output, ejection fraction and fractional shortening in a dose-dependent manner. A UPLC-QTOF-MS-based serum metabolomics approach was applied to explore the latent mechanism. A total of 25 differentiated metabolites and 8 perturbed metabolic pathways were identified. These results indicated that pyxinol fatty acid ester derivatives 2e and 3b might be considered as potent drug candidates against heart failure and deserved further research and development.

A new alkynol compound from Platycodins folium and its cytotoxicity.

A new alkynol, platycodynol (1), identified as 2, 3, 9, 13, 14-pentahydroxy-4, 6-tetradecadiyne, along with six known compounds (2-7) were obtained from Platycodins folium for the first time. Their structures were elucidated with infrared (IR), ultraviolet (UV), 1D and 2D nuclear magnetic resonance (NMR) spectroscopic analysis as well as by high resolution electrospray ionization mass spectroscopy (HRESIMS). Platycodynol showed cytotoxicity against S180, A549 and SPC-A-1 cancer cells but no cytotoxicity against normal cells NCTC1469 and HL-7702 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method.

In vivo pharmacokinetics, distribution, and excretion of an anticancer agent isolated from red ginseng, in rat.

The compound 20(S),25-epoxydammarane-3ß,12ß,24α-triol (24-hydroxy-panaxadiol or 24-OH-PD), isolated from the red Panax ginseng CA Meyer possesses anticancer activity. Our aim was to study the pharmacokinetic characteristics of 24-OH-PD, which is essential for pre-clinical research during the development of new drugs. In this study, a simple and sensitive ultra-performance liquid chromatography-mass spectrometry (LC-MS/MS) method was established and used for studying the pharmacokinetics, in vitro protein binding, tissue distribution, and elimination profiles of 24-OH-PD in rats. 24-OH-PD was characterized by linear pharmacokinetics in the dose range of 2.5-10 mg/kg and had relatively longer half-life (4.82-5.45 h) than the other ginsenosides. It had a wide tissue distribution profile in rats and was primarily distributed in the lung. Within 96 h of intravenous administration, 13.84% of 24-OH-PD was excreted out via feces and 0.02% via urine in its unchanged form. In conclusion, a simple LC-MS/MS method with high sensitivity and selectivity was established for the quantification of 24-OH-PD.