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Ilex pubescens Hook. et Arn (IP), traditionally known for its properties of promoting blood circulation, swelling and pain relief, heat clearing, and detoxification, has been used in the treatment of thromboangiitis obliterans (TAO). Despite its traditional applications, the specific mechanisms by which IP exerts its therapeutic effects on TAO remain unclear. This study aims to uncover the underlying mechanisms in the therapeutic effects of IP on TAO, employing network pharmacology and metabolomic approaches. In this study, a rat TAO model was established by injecting sodium laurate through the femoral artery, followed by the oral administration of IP for 7 days. Plasma coagulation parameters were measured to assess the therapeutic effects of IP. The potential influence on the femoral artery and gastrocnemius muscle was histopathologically evaluated. Network pharmacology was employed to predict relevant targets and model pathways for TAO. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was used for the metabolic profile analysis of rat plasma. Immunohistochemistry (IHC) was used to verify the mechanisms by which IP promotes blood circulation in TAO. The study revealed that IP improved blood biochemical function in TAO and played a significant role in vascular protection and maintaining normal blood vessels and gastrocnemius morphologies. Network pharmacology showed that IP compounds play a therapeutic role in modulating lipids and atherosclerosis. Metabolomic analysis revealed that the pathways involved in sphingolipid metabolism and steroid biosynthesis were significantly disrupted. The joint analysis showed a strong correlation between lysophosphatidylcholine and IP components, including triterpenoid and iridoid components, which support the curative action of IP through the modulation of sphingolipid metabolism. Furthermore, decreased expression levels of SPHK1/S1PR1, TNF-α, IL-1β, and IL-6 were observed in the IP-treated group, suggesting that IP exerts a protective effect on the vasculature primarily by regulating of the SPHK1/S1PR1 signaling pathway. In this study, we found that IP protects the vasculature against injury and treats TAO by regulating the steady-state disturbance of the sphingolipid pathway. These findings suggest that IP promotes vasculature by modulating sphingolipid metabolism and SPHK1/S1PR1 signaling pathway and reduce levels of inflammatory factors, offering new insights into its therapeutic potential. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two previously undescribed and one new natural polyketides were isolated. • All compounds (except 4 , 6 and 7) were firstly reported from Chaetomium sp. • Compound 1 − 4 were identified as derivatives of shikimic acid. Two undescribed shikimic acid derivatives named shikimerans B and C (1 and 2), one new natural compound shikimeran D (3), as well as five known compounds 4 − 8 were obtained from the EtOAc extract of the endophytic fungus Chaetomium sp. FZ-4. Their structures were determined by the NMR spectroscopy and HRESIMS examination, while the absolute configurations of compounds 1 − 3 were clarified based on the electronic circular dichroism (ECD) experiment. These new compounds enriched the structural diversity of shikimic acid analogues and also expanded the chemical diversity of the metabolites of Chaetomium sp.. [ABSTRACT FROM AUTHOR]

Abstract High melting temperature and viscosity of most benzoxazine monomers are challenging problems in processing, especially for preparation of composites. The present work introduces the "reactive diluent" concept to improve the processability of benzoxazines. A benzoxazine monomer having a vinyl group is first synthesized from 4-vinylguaiacol (4VG), and then dissolved in a reactive diluent, styrene or methyl methacrylate. The resulting solutions show low viscosity (less than 2 mPa s), and exhibit high reactivity during free radical and ring-opening polymerizations, successively. Furthermore, the solutions are applied to fabricate cotton fabrics reinforced composites. Both of them possess high glass transition temperature and excellent mechanical properties, which have potential applications as structural components. Graphical abstract Styrene and methyl methacrylate can be a good "reactive diluent" to improve processability of the benzoxazine derived from 4-vinlyguiacol. Image 1 Highlights • The "reactive diluent" concept is transferred to benzoxazine applications, leading to largely improved processability. • A benzoxazine monomer having a vinyl group is first synthesized from bio-based materials. • Mixture of the benzoxazine and the reactive diluent shows low viscosity and high reactivity for polymerizations. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The Dengzhan Shengmai capsule (DZSM) is known in China for its remarkable curative effect as a treatment of cardiovascular diseases, such as coronary heart disease and ischemic stroke. DZSM is a Chinese herbal compound preparation that consists of four ingredients, including Erigeron breviscapus (Vaniot) Hand.-Mazz., Panax ginseng C.A. Mey, Ophiopogon japonicas (Thunb.) Ker-Gawl. and Schisandra chinensis (Turcz.) Baill., and was indexed in the Chinese Pharmacopoeia 2010. DZSM and clopidogrel are often co-prescribed in the clinic to prevent the recurrence of stroke or other cardiovascular and cerebrovascular diseases. However, the effect of DZSM on the pharmacokinetics of clopidogrel remains unclear. Aim of the study The purpose of the study is to explore the pharmacokinetics and potential interaction between DZSM and clopidogrel and the underlying mechanism. Materials and methods Rats were used to investigate the effect of DZSM on the pharmacokinetics of clopidogrel and its active metabolite in vivo . The plasma concentrations were simultaneously determined using LC–MS/MS. The effects of DZSM on the P-gp-mediated efflux transport and CYP450-mediated metabolism of clopidogrel were investigated using MDCKII-MDR1 cells and rat liver microsomes, respectively. Results After pretreatment with DZSM, the C max and AUC 0–∞ of clopidogrel increased from 0.4±0.1 to 1.7±0.6 ng/mL and 0.9±0.4 to 2.0±0.2 ng/mL h, respectively. The C max and AUC 0–∞ of the derivatized active metabolite of clopidogrel decreased from 8.2±1.2 to 2.8±0.5 ng/mL and 18.2±5.6 to 6.4±3.7 ng h/mL, respectively. In MDCKII-MDR1 cells, the P-gp-mediated efflux transport of clopidogrel was significantly inhibited by the DZSM extract. In rat liver microsomes, DZSM inhibited clopidogrel metabolism with an IC 50 of 0.02 mg/mL. Conclusions DZSM significantly affects the pharmacokinetics of clopidogrel and its active metabolite by inhibiting the P-gp-mediated efflux transport and CYP450-mediated metabolism of clopidogrel. Thus, caution is needed when DZSM is co-administered with clopidogrel in the clinic because the interaction of these drugs may result in altered plasma concentrations of clopidogrel and its active metabolite. [ABSTRACT FROM AUTHOR]

Two new hydroxylated ent -kauranoic acids, pterisolic acid G ( 1 ) and pterisolic acid H ( 3 ), together with five known ent -kaurane-type diterpenoids ( 2 and 4 – 7 ) were isolated from the whole plant of Pteris semipinnata L. The structures of compounds 1 – 3 were elucidated on the basis of HR-MS, 1D and 2D NMR analysis, and the absolute configuration of compounds 1 and 2 were determined by the results of single crystal X-ray diffraction experiment. Compounds 1 – 4 and 6 – 7 were evaluated in vitro cytotoxicity against the A549, CT26.WT, and Hep G2 cells, and compounds 4 and 6 possessed varying degrees of activity. [ABSTRACT FROM AUTHOR]

Background: Tanshinone IIA (Tan), the main active component of Salvia miltiorrhiza, has been demonstrated to have antioxidant activity. Acetaminophen (APAP), a widely used antipyretic and analgesic, can cause severe hepatotoxicity and liver failure when taken overdose. Oxidative stress has been reported to be involved in APAP-induced liver failure.Purpose: This study aimed to investigate the effect of Tan on APAP-induced hepatotoxicity and the underlying mechanisms involved.Study Design: C57BL/6J mice were divided into six groups: (1) control, (2) APAP group, (3) APAP+Tan (30mg/kg) group, (4) Tan (30mg/kg) group, (5) APAP+Tan (10mg/kg) group, (6) Tan (10mg/kg) group. Mice in group 3 and 5 were pre-treated with specified dose of Tan by gavage and subsequently injected with an overdose of APAP intraperitoneally (i.p., 300mg/kg). The effect of Tan on Nrf2 pathway was investigated in HepG2 cells and mice.Methods: Plasma aspartate transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), liver glutathione (GSH), glutathione transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) levels were determined after mice were sacrificed. Lipid peroxidation and histological examination were performed. The effect of Tan on the Nrf2 pathway was detected by western blotting and qRT-PCR.Results: Tan pretreatment reduced APAP-induced liver injury. Tan was able to activate Nrf2 and increase the expression levels of Nrf2 target genes, including glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H:quinine oxidoreductase 1 (NQO1) and hemeoxygenase-1 (HO-1), in a dose-dependent manner in HepG2 cells. Consistent with our observations in HepG2 cells, Tan increased nuclear Nrf2 accumulation and upregulated mRNA and protein levels of the Nrf2 target genes GCLC, NQO1 and HO-1 in C57BL/6J mice compared with mice treated with APAP alone.Conclusions: Our results demonstrate that Tan pretreatment could protect the liver from APAP-induced hepatic injury by activating the Nrf2 pathway. Tan may provide a new strategy for the protection against APAP-induced liver injury. [ABSTRACT FROM AUTHOR]

The brake thermal efficiency and exhaust emission issues are still not fully-resolved to diesel/natural gas dual fuel engines. To better understand the effect of pilot diesel ignition mode on combustion and emissions characteristics of dual fuel engines, a detailed study concerned with diesel injection timing was conducted. The testing work was operated on a 6-cylinder turbocharged intercooler diesel/natural gas dual fuel heavy-duty engine at light load operations, and diesel injection timing was controlled over a very wide range. The investigated results show that the diesel injection timing ( T inj ) has an obvious effect on pilot diesel ignition mode. A significant advancing T inj leads to pilot diesel ignition mode differs from traditional diesel engine compression ignition mode in the sense that it does not occur at a specific place in the spray, which is a two-stage autoignition mode. With advancing T inj , engine combustion and emissions characteristics, including cylinder pressure, cylinder temperature, heat release rate, start of combustion (SOC), ignition delay, combustion duration, crank angle of 50% heat release (CA50), nitrogen oxides (NOx) and total hydrocarbon (THC), show completely different variation trends in different ignition modes. Overall, higher thermal efficiency and lower emissions can be achieved simultaneously in two-stage autoignition mode. Satisfactory results can be obtained with higher brake thermal efficiency (35%), lower NOx (60 ppm) and THC (0.4%) emissions, when T inj is 42.5 °CA BTDC. [ABSTRACT FROM AUTHOR]

Purpose We investigated the feasibility of using Gamma Knife (GK) radiosurgery for “dose painting” to deliver higher doses to residual or recurrent nodules and surgical cavity after resection of brain metastases. Methods and materials Two integrated boost techniques were developed with GK. The single-target technique delineated both the surgical cavity (cavity) and gross disease (nodule) as a single target. Dose was prescribed to the target with the goal of covering the nodule with a higher dose. The 2-target technique delineated the cavity and nodule as separate target volumes, each prescribed to its own dose and planned separately. Two cases were used to illustrate each technique. The single-target technique was used to deliver 16 Gy to a smaller cavity (7 cm 3 ) and a 20-Gy integrated boost to 2 nodules (case 1). The 2-target technique was used to deliver 12 Gy to a larger cavity (21.5 cm 3 ) and 20 Gy to a single nodule (case 2). Results For both cases, the cavity coverage with the prescribed dose was 100% with the standard plan and integrated boost techniques. For case 1, compared with a standard plan, the single-target technique improved the 20-Gy nodule coverage from 89.7% (nodule 1) and 97.9% (nodule 2) to 100% (both) and increased the minimum dose from 16.6 Gy to 20.8 Gy (nodule 1) and from 19.4 Gy to 20.8 Gy (nodule 2). For case 2, compared with a standard plan, the 2-target technique improved the 20-Gy nodule coverage from 4% to 100% and the minimum dose from 13.8 Gy to 21 Gy. Conclusions Both GK integrated boost approaches allowed for effective delivery of higher doses to residual or recurrent nodules in a surgical cavity. In our experience, the single-target technique works well for small cavities, whereas the 2-target technique is well suited for larger cavities. [ABSTRACT FROM AUTHOR]

Background Triptolide, an active ingredient extracted from the Chinese herb Tripterygium wilfordii Hook f., has multiple pharmacological properties, including anti-inflammatory, immune-modulatory, and anti-proliferative activities. However, the hepatotoxicity of triptolide always limits its clinical applications. Hypothesis/Purpose Farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays a key role in hepatoprotection through the maintenance of liver metabolism homeostasis. This study explored the role of FXR in triptolide-induced cytotoxicity and investigated whether activation of FXR can protect against triptolide-induced liver injury. Study design The role of FXR in triptolide-induced cytotoxicity was investigated in HepG2 cells. In addition, the protective effect of the selective FXR agonist GW4064 on triptolide-induced hepatotoxicity was explored in BALB/c mice. Methods HepG2 cells were transient transfected with FXR expression plasmid or FXR-siRNA. The cytotoxicity was compared using the MTT assay. The extent of liver injury was assessed by histopathology and serum aminotransferases. The expression of FXR and its target genes were detected by Western blot and qRT-PCR. Results The transient overexpression of FXR protected against triptolide-induced cell death, whereas FXR knockdown with a specific small interfering RNA resulted in increased cytotoxicity. In BALB/c mice, treatment with the FXR agonist GW4064 attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and lipid peroxidation. Moreover, the livers of GW4064-treated mice showed increased expression of FXR and several related target genes involved in phase II and phase III xenobiotic metabolism. Conclusion Taken together, these results indicate that activation of FXR attenuates triptolide-induced hepatotoxicity and provide direct implications for the development of novel therapeutic strategies against triptolide-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Two new ursane-type triterpene saponins, 3- O -β- d -glucopyranosyl(1 → 3)-[α- l -rhamnopyranosyl(1 → 2)]-α- l -arabinopyranosylurs-12,19(29)-dien-28-oic acid 28- O -α- l -rhamnopyranosyl(1 → 2)-β- d -glucopyranosyl ester ( 1 ) and 3- O -β- d -glucopyranosyl(1 → 3)-[α- l -rhamnopyranosyl(1 → 2)]-α- l -arabinopyranosyl-19α,20α-dihydroxyurs-12-en-28-oic acid 28- O -α- l -rhamnopyranosyl(1 → 2)-β- d -glucopyranosyl ester ( 2 ), along with thirteen known triterpene saponins were isolated from the n -BuOH part of the MeOH extraction of the leaves of Ilex kudingcha C.J. Tseng (also called “Ku-Ding-Cha”). The structures of new compounds were elucidated on the basis of detailed spectroscopic analysis, including HR-ESI-TOF-MS, 1D and 2D-NMR experiments, and by acid hydrolysis. All the compounds were screened for antiplatelet aggregation activity in vitro , and compounds 1 , 2 , 3 , 7 , 12 and 15 showed significant inhibition of platelet aggregation induced by ADP (5 μM) with IC 50 values of 14.7 ± 3.7, 11.3 ± 2.5, 17.4 ± 4.6, 20.5 ± 3.1, 8.1 ± 1.5 and 18.9 ± 4.2 μM, respectively. [ABSTRACT FROM AUTHOR]

Cisplatin is a potent anti-cancer agent for various types of tumors. However, the clinical use of cisplatin is often limited by its nephrotoxicity. This study reports that WZ tablet (WZ, a preparation of an ethanol extract of Schisandra sphenanthera ) mitigates cisplatin-induced toxicity in renal epithelial HK-2 cells and in mice. Pretreatment of HK-2 cells with WZ ameliorated cisplatin-induced cytotoxicity caused by oxidative stress, as was demonstrated by reductions in the levels of reactive oxygen species (ROS) and increased levels of glutathione (GSH). WZ facilitated the nuclear accumulation of the transcription factor NF-E2-related factor 2 (Nrf2) and the subsequent expression of its target genes such as NAD(P)H:quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1) and glutamate cysteine ligase (GCL). Protective effects of WZ on cisplatin-induced nephrotoxicity were also observed in mice. WZ attenuated cisplatin-induced renal dysfunction, structural damage and oxidative stress. The nuclear accumulation of Nrf2 and its target genes were increased by WZ treatment. Taken together, these findings demonstrated WZ have a protective effect against cisplatin-induced nephrotoxicity by activation of the Nrf2 mediated defense response, which is of significant importance for therapeutic intervention in cisplatin induced renal injury. [ABSTRACT FROM AUTHOR]

Background: Blood stasis syndrome (BSS) is a severe disorder involving disturbances in glycerophosphocholine metabolism. Ilex pubescens (IP) can regulate the levels of lipids, such as lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE); however, the main active constituent of IP and its corresponding mechanism in BSS treatment are still unclear.Purpose: To explore the mechanisms by which triterpenoid saponins of IP (IPTS) promote blood circulation using system pharmacology-based approaches.Methods: Sprague-Dawley (SD) rat BSS model was prepared by oral administration of IPTS for 7 days followed by adrenaline hydrochloride injection before immersion in ice water. Coagulation parameters in plasma and thromboxane B2 (TXB2), endothelin (ET) and 6-keto-PGF1α in serum were measured. The possible influence on abdominal aortas was evaluated by histopathology assessment. Human vein endothelial cells (HUVECs) were incubated with ox-LDL, and the effects of IPTS on cell viability and LDH release were investigated. UPLC-QTOF-MS/MS was used for metabolic profile analysis of lipid-soluble components in rat plasma and intracellular metabolites in HUVECs. Network pharmacology was used to predict the relevant targets and model pathways of BSS and the main components of IPTS. Molecular docking, molecular dynamics (MD) simulation and biochemical assays were used to predict molecular interactions between the active components of IPTS and target proteins. RT-PCR was used to detect the mRNA level of target proteins. Western blotting and immunohistochemistry (IHC) were used to verify the mechanisms by which IPTS promotes blood circulation in BSS.Results: IPTS improved blood biochemical function in the process of BSS and played a role in vascular protection and maintenance of the normal morphology of blood vessels. Furthermore, metabolite pathways involved in steroid biosynthesis and sphingolipid metabolism were significantly perturbed. Both metabolomics analysis and network pharmacology results showed that IPTS ameliorates vascular injury and that lipid accumulation may be mediated by PI3K/AKT signaling pathway activation. MD simulation and enzyme inhibitory activity results suggested that the main components of IPTS can form stable complexes with PI3K, AKT and eNOS and that the complexes have significant binding affinity. PI3K, AKT, p-AKT, and eNOS mRNA and protein levels were considerably elevated in the IPTS-treated group. Thus, IPTS protects the vasculature by regulating the PI3K/AKT signaling pathway, activating eNOS and increasing the release of NO.Conclusion: A possible mechanism by which IPTS prevents BSS is proposed: IPTS can promote blood circulation by modulating sphingolipid metabolism and activating the PI3K/AKT/eNOS signaling pathways. [ABSTRACT FROM AUTHOR]

Abstract: A novel anthocyanidin glycoside, abacopterin J (1), together with the known eruberin B (2) and eruberin C (3) was isolated from the fern Abacopteris penangiana (Hook.) Ching. The structure of the new compound 1 was elucidated on the basis of extensive spectroscopic analysis, including HSQC, HMBC, 1 H– 1 H COSY and ROESY, and chemical evidence. Abacopterin J is the first example of an anthocyanidin glycoside isolated from natural sources, which is comprised of a flavan and an anthocyanidin moiety. [Copyright &y& Elsevier]

Abstract: Monte Carlo simulations of heavy ion interactions using the Geant4 toolkit were compared with measurements of energy deposition in a spherical tissue-equivalent proportional counter (TEPC). A spherical cavity with a physical diameter of 12.7mm was filled with propane-based tissue-equivalent gas surrounded by a wall of A-150 tissue-equivalent plastic that was 2.54mm to thick. Measurements and Monte Carlo simulations were used to record the energy deposition and the trajectory of the incident particle on an event-by-event basis for ions ranging in atomic number from 2 (4He) to 26 (56Fe) and in energy from 200MeV/nucleon to 1000MeV/nucleon. In the simulations, tracking of secondary electrons was terminated when the range of an electron was below a specified threshold. The effects of range cuts for electrons at 0.5μm, 1μm, 10μm, and 100μm were evaluated. To simulate an energy deposition influenced by large numbers of low energy electrons with large transverse momentum, it was necessary to track electrons down to range cuts of 10μm or less. The Geant4 simulated data closely matched the measured data acquired using a TEPC for incident particles traversing the center of the detector as well as near the gas-wall interface. Values of frequency mean lineal energy and dose mean lineal energy were within 8% of the measured data. The production of secondary particles in the aluminum vacuum chamber had no effect on the response of the TEPC for 56Fe at 1000MeV/nucleon. The results of this study confirm that Geant4 can simulate patterns of energy deposition for existing microdosimeters and is valuable for improving the design of a new generation of detectors used for space dosimetry and for characterizing particle beams used in hadron radiotherapy. [Copyright &y& Elsevier]

This paper presents a method for estimating parameters of a two-layer stratified ocean using satellite SAR images. According to weak nonlinearity shallow water theory, internal solitary waves (ISWs) in stratified oceans may be either depression or elevation waves, depending on the sign of the quadratic nonlinearity coefficient in the KdV equation. It has been confirmed that ISWs can convert their polarity when passing through a turning point, where the quadratic nonlinearity coefficient changes sign. For a two-layer stratified ocean, the turning point is located where the upper and lower layer depths are equal. The authors suggest that depression, elevation and broadening ISWs can be discerned according to their different signatures in SAR images. It is also found that a SAR image can record a continuous evolution process from depression to elevation ISWs in its spatial domain, under conditions of a spatially inhomogeneous ocean environment. Therefore, the upper and lower layer depths can be calculated by determining the polarity conversion of ISWs observed in satellite SAR images. Furthermore, the density difference between the upper and lower layers can also be estimated, when the wave speed is known. We extract ocean stratification parameters, including upper layer depth and density difference, from polarity conversion of ISWs observed in a RADARSAT-1 SAR image taken over the northeastern South China Sea. Comparing the estimated results with field measurements, we find that this method can estimate the upper layer depth with considerable success. In estimating the density difference between the upper and lower layers, it also gives a quite reasonable result. [Copyright &y& Elsevier]

Background: Croton crassifolius Geisel (CCG, also known as Ji-Gu-Xiang in Traditional Chinese Medicine), is traditionally prescribed for the therapy of rheumatic arthritis and gastrointestinal ulcer. However, the effect of CCG on ulcerative colitis (UC) has not been investigated.Purpose: To explore the therapeutic potential and underlying mechanism of CCG extract against UC by colonic and serum metabolomics.Methods: In order to standardize the CCG extract, UPLC-QTOF-MS was used for quantitative and qualitative analysis of the representative terpenoids. C57BL/6J mice were divided into control, Dextran Sulfate Sodium (DSS), mesalazine (100 mg•kg-1), CCG extract (150 and 600 mg•kg-1) groups. The mice were provided 3% DSS dissolved in distilled water ad libitum for 7 days except control group. Weight change, disease activity index (DAI), colon lengths and expression of inflammatory mediators iNOS and COX-2 in colonic tissue were determined. Serum and colon metabolomics using UPLC-QTOF-MS technology coupled with multivariate data analysis were performed to reveal the underlying mechanism.Results: Thirty-five terpenoids in CCG were identified by fingerprint, in which ten representative terpenes were quantified. CCG could relieve the weight loss, the degree of bloody stool and ulcer of colon, as well as significantly lowering the expression level of iNOS and COX-2. Metabolomics analysis showed that 25 biomarkers were obviously interfered by CCG treatment and 16 of them were highly correlated with the efficacy of CCG. The analysis of metabolic pathway showed that the anti-UC effect of CCG was associated with the regulation on linoleic acid metabolism, sphingolipid metabolism, α-linolenic acid metabolism, and glycerophospholipids metabolism.Conclusions: The oral administration of CCG significantly alleviated DSS-induced UC symptoms by reducing inflammation and rectifying the metabolic disorder. CCG may provide a new strategy for the management of UC. [ABSTRACT FROM AUTHOR]

Croton crassifolius Geisel. (C. crassifolius), belonging to the family Euphorbiaceae, is a traditional Chinese medicine primarily distributed in Asia. This medicinal plant is commonly used for moving qi and relieving pain, dispelling wind and swelling, relaxing tendons and activating collaterals in traditional Chinese medicine (TCM) to treat rheumatic arthritis, bruises and injuries, gastric and duodenal ulcers, sore throat, and so on. To date, no comprehensive review on C. crassifolius has been published. The purpose of this review is to provide a thorough overview of the botany, traditional uses, phytochemistry, pharmacology, and quality control of C. crassifolius. We mainly focus on phytochemical and pharmacological investigations of C. crassifolius. Furthermore, perspectives for possible future studies on C. crassifolius are also discussed. A thorough search of published articles up to May 2023 was conducted, focusing on original publications related to C. crassifolius, using numerous literature databases, including China National Knowledge Infrastructure (CKNI) (http://www.cnki.net), PubMed Database (https://pubmed.ncbi.nlm.nih.gov), Wanfang Data (http://www.wanfangdata.com.cn/), and Web of Science database (http://apps.webofknowledge.com/). More than 250 chemical compounds, including terpenoids, volatile oils, pyran-2-one derivatives, and flavonoids have been isolated and identified from C. crassifolius. Among these compounds, terpenoids form the main components. Modern pharmacological studies have shown that the plant possesses antiangiogenic, anti-inflammatory, antitumor, antibacterial, and antiviral properties. After the initial search, we reviewed the deficiencies of pharmacological mechanism and quality control studies and suggested workable solutions, which will be of great use in future research. In this review we have conducted a thorough overview of C. crassifolius and offered new perspectives on research regarding quality control, substance basis, and pharmacological mechanism, providing theoretical guidance for the clinical application and development of Chinese medicine. However, several defects, such as pharmacological mechanism determination, quality control, pharmacokinetic establishment, and toxicology assessment of C. crassifolius need further study. [Display omitted] • The study first discussed quality control, which has not been explored in previous reviews. • The study first reviewed the limitations of pharmacological mechanism and quality control studies and proposed appropriate solutions, which are of great practical significance to subsequent studies. • This is the first systematic critical review of studies on Croton crassifolius Geisel. [ABSTRACT FROM AUTHOR]

Abstract: At the University of Cincinnati Nuclear and Radiological Engineering Program, a once moth-balled vintage subcritical reactor facility was reassembled to provide a practical laboratory experience for students in nuclear science. The relative simplicity and accessibility of this facility are some of its most desirable features. Recent work had led to supplementing the experimental aspects of this facility with a three-dimensional, full detail, MCNP model of this reactor. This article emphasizes the latest validations of this simulation model against the most recently available laboratory measurements of neutron flux distributions and subcritical neutron multiplication factors, while illustrating a unique feature of this facility which enables experimentalists to carry out step by step measurements, and the corresponding simulations, while the core is being loaded and unloaded. Furthermore, additional simulations are herein included to evaluate the impact of different moderator and reflector arrangements upon core reactivity, including a few combinations of heavy water and/or beryllium, primarily as a venue for researchers to begin studying potential upgrades or changes to the current design. [Copyright &y& Elsevier]

Internal solitary waves (ISWs) make important contributions to the energy cascade, ocean mixing and material transport in the ocean. However, there are few observational studies on the vertical structure of ISWs. In this article, we describe and analyze 11 ISWs near Dongsha Atoll in the South China Sea directly observed using two-dimensional seismic data. We calculate the vertical structures of these ISWs, and compared them with two theories. We find that three ISWs conform to the linear vertical structure function, four conform to the first-order nonlinear vertical structure function, and the remaining conform to neither function. We use the empirical mode decomposition (EMD) method to analyze reasons for the difference between the observed and theoretical vertical structures. The results show that the vertical structure is mainly determined by nonlinearity, which is an important dynamic characteristics of ISW. Therefore, whether the theory conforms to the observation depends on the ability of theory to describe the nonlinear characteristics of ISWs. In addition, topography and background flow affect the vertical structure. • The seismic oceanography can observe the fine vertical structure of ISW. • The vertical structure of ISW is mainly determined by nonlinearity. • The vertical structure of ISW may be affected by its own amplitude, water depth, topography and background flow. • Eddy can reduce the amplitude of ISW and affect the vertical structure. [ABSTRACT FROM AUTHOR]

Two new compounds eutyditerpenoid A (1) and seco-phenochalasin B (5), together with seven known compounds diaporthein A (2), aspergillon A (3), phenochalasin B (4), cytochalasins Z 24 and Z 25 (6 and 7), scoparasins A and B (8 and 9) were isolated from marine-derived Eutypella scoparia GZU-4-19Y. Among them, eutyditerpenoid A (1) with a rare 6/7/6 ring system possesing an anhydride moiety was the first example in the pimarane-type diterpenoids. Their structures were determined based on spectroscopic methods and the electronic circular dichroism (ECD) calculations. In the bioassays, all of the isolates were evaluated for their inhibitory activity against NO production induced by lipopolysaccharide in RAW 264.7 cells. Compounds 3 and 7 showed potent NO inhibition activity with IC 50 values of 2.1 and 17.1 μM respectively, and the former also significantly suppressed the protein expression of iNOS and COX-2 at the concentration of 2.5 μM. [Display omitted] • An undescribed diterpenoid (1) possesed a rare 6/7/6 ring system with an anhydride moiety. • The absolute configuration of new compounds was established by ECD calculations. • Aspergillon A inhibited the expression of pro-inflammatory enzymes iNOS and COX-2. [ABSTRACT FROM AUTHOR]

Six undescribed meroterpenoids aspertermeroterpenes A−F and four known analogues were isolated from the marine-derived fungus Aspergillus terreus GZU-31-1. Their structures were elucidated based on spectroscopic methods and electronic circular dichroism calculations. All meroterpenoids possessed the unique acetyl group at C-11, and also aspertermeroterpene A featured the rare C-14 decarboxylated in DMOA meroterpenoids. In the bioassays, aspermeroterpene B exhibited a potent inhibitory effect on the activation of hepatic stellate cells at the concentration of 5 μM via targeting the Nrf2 signaling. This is the first time reported that aspermeroterpene B as a previously undescribed carbon skeleton of meroterpenoid possessed anti-liver fibrosis effect. Six undescribed meroterpenoids from the Marine-derived fungus Aspergillus terreus GZU-31-1 and aspermeroterpene B exerts anti-liver fibrosis effects by targeting Nrf2 signaling pathway in vitro. [Display omitted] • Six undescribed meroterpenoids isolated from the fungus A. terreus GZU-31-1. • The absolute configuration of meroterpenoids were established by ECD calculations. • Aspermeroterpene B possessed anti-liver fibrosis effect at 5 μM. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacology relevance Rhubarb Peony Decoction (RPD) is a formula of traditional Chinese medicine chronicled in Jin Gui Yao Lve , commonly used to treat ulcerative colitis (UC). However, the underlying mechanism of RPD treating UC remains elusive. In our study, we investigated the therapeutic efficacy of RPD and potential mechanism involved in inhibiting dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. Methods The colitis was induced by DSS in mice for 5 days and estimated body weight loss, disease activity index (DAI) and colon length. Histological changes were observed by H&E staining. The number and abundance of gut mircrobiota were measured with 16 S rDNA sequencing. GC-MS was used to detect the concentration of short chain fatty acids (SCFAs) in cecum. Flow cytometry analyzed the proportion of Th17 and Treg cells in mesenteric lymph nodes (MLNs). IL-17A and Foxp3 in colon were determined by immunohistochemical analyses. The level of cytokine was determined by Multi-Analyte Flow Assay Kit. Results Administration of RPD significantly alleviated the pathological changes of UC mice, involving rescued the inflammation-related reduction of colon length, ameliorated body weight loss and damaged tissue. In addition, RPD altered the gut microbiota, involving restored α diversity, increased significantly the abundance of Firmicutes and Actinobacteria, decreased the Proteobacteria and Bacteroidetes. Furthermore, the number of Butyricicoccus pullicaecorum, a butyrate-producing bacterium, were augmented obviously by RPD. Besides, RPD restored the content of SCFA in intestinal tract. Additionally, the proportion of Th17 cells and Treg cells in mesenteric lymph nodes, likewise, the expression of IL-17A and Foxp3 in colon were regulated by RPD, contributing to the restoration of Th17/Treg balance. Moreover, RPD significantly decreased the level of IL-6, TNF-α, IFNγ, IL-10, IL-17A, IL-21, IL-22 in colon, simultaneously increased Treg-related cytokine TGF-β at dose-dependently. Conclusions These results demonstrated that RPD had effect on ulcerative colitis, which was related to regulating gut microbiota, especially Butyricicoccus pullicaecorum, and SCFAs to restore the gut Th17/Treg homeostasis. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Ilex pubescens Hook. et Arn (MDQ), a traditional Chinese herb, is used in the treatment of cardiovascular diseases. However, the mechanisms underlying the preventive effect of MDQ on blood stasis remain unclear. Aim of the study In this study, serum metabolomics integrated with a biochemical assay strategy were established to evaluate the preventive effect and mechanism of action of MDQ on rats with acute blood stasis. Materials and methods Forty-nine rats were divided into seven groups: the control group, model group, aspirin treatment group (30 mg/kg), clopidogrel treatment group (8 mg/kg) and three MDQ treatment groups (250, 500 and 1000 mg/kg). A hybrid quadrupole time of flight mass spectrometry (QTOF/MS) coupled to ultra-high-performance liquid chromatography (UPLC) was applied for profiling the serum metabolites. The multivariate data analysis techniques using unsupervised principal component analysis (PCA) and supervised orthogonal projections to latent structures discriminant analysis (OPLS-DA) were used for pattern recognition and distinguishing variabilities among groups. Results MDQ protected the rats against blood stasis, as evidenced by the restoration of the anti-platelet aggregation activity, fibrinogen concentration, prothrombin time, thrombin time, activated partial thromboplastin time, endothelial nitric oxide synthase, endothelin, thromboxane B 2 and 6-keto-prostaglandin F1 α. The combination of PCA and OPLS-DA revealed deviations in eighteen differential biomarkers in serum. The identified biomarkers were primarily engaged in the metabolic pathways including arachidonic acid metabolism, glycerophospholipid metabolism, phospholipid biosynthesis and bile acid biosynthesis. The levels of eleven biomarkers showed significant alterations and a tendency to be restored to normal values in MDQ-treated blood stasis rats. Moreover, a correlation network diagram was constructed to show the serum biomarkers perturbed by MDQ. Conclusions These results suggested that MDQ had preventive effects on blood stasis in rats via arachidonic acid metabolism and glycerophospholipid metabolism. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Triterpenoids, the major bioactive ingredients of Ilicis Rotundae Cortex, contributes a significant cardiovascular protection activity. Although many studies about the total saponins have been reported, the absorption triterpenoids and pharmacokinetic behaviors were unclear. Thus, the present study aims to comprehensive elucidate the absorption triterpenoids and their pharmacokinetics in rats after oral administration the crude extract using UPLC/Q-TOF-MS/MS. A total of forty-two triterpenoids were successfully characterized from the rat plasma, and thirty-two of them were validated by the reference substances, while the others were tentatively identified based on the mass spectral fragmental patterns. Furthermore, the plasma concentrations of six absorption bioactive triterpenoids (rotundinoside C, ilexoside O, pedunculoside, rotundic acid, rotundanonic acid and ilexgenin A) were simultaneously quantified by selected reaction monitoring in negative ionization mode. All analytes exhibited good linearity with correlation coefficients values greater than 0.99 and the LLOQ ranged from 1.2 to 3.2 ng/mL, and method validation for selectivity, precision, accuracy, recovery, matrix effect and stability were reckoned acceptable. The results were successfully applied for the multiple-component pharmacokinetic study of the six bioactive triterpenoids. [ABSTRACT FROM AUTHOR]

Tripterygium wilfordii polyglycosides (TWP), extracted from the traditional Chinese herb Tripterygium wilfordii , has been widely used in the treatment of rheumatoid arthritis (RA). However, the toxicity of TWP to a variety of organs such as liver, kidney and testis greatly limits its clinical application. Salvia miltiorrhiza Bunge is often used in the treatment of RA due to its blood circulation promoting, stasis resolving, and anti-inflammatory effects. Salvia miltiorrhiza Bunge has also been reported to possess multiple organ protective effects. To investigate the influences of two main components of Salviorrhiza miltiorrhiza Bunge, hydrophilic salvianolic acids (SA) and lipophilic tanshinones (Tan), on the efficacy and toxicity of TWP in treating RA and to explore the underlying mechanisms. SA and Tan were extracted from Salvia miltiorrhiza Bunge and the extracts were quantitated by HPLC and identified by UPLC-Q/TOF-MS. Then, a collagen-induced arthritis (CIA) rat model was established using bovine type II collagen (CII) and incomplete Freund's adjuvant (IFA). CIA rats were treated with TWP and/or SA/Tan. After 21 days of continuous treatment, arthritis symptoms and organs toxicity were evaluated. Meanwhile, serum metabolomics were investigated by the UPLC-Q/TOF-MS to understand the underlying mechanism. SA and Tan extracts could significantly alleviate arthritis symptoms in CIA rats and decrease the serum levels of inflammatory factors TNF-α, IL-1β and IL-6 when combined with TWP. Meanwhile, both extracts alleviated injury of liver, kidney and testis caused by TWP, and the hydrophilic extract SA was superior. Moreover, a total of 38 endogenous differential metabolites were identified between the CIA model group and the TWP group, among which 33 metabolites were significantly recovered after the combination of SA or Tan. Metabolic pathway analysis showed that SA and Tan can affect metabolic pathways including linoleic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and steroid biosynthesis metabolism pathway. Our findings indicated for the first time that two Salviorrhiza miltiorrhiza Bunge extracts could improve the efficacy and reduce the toxicity of TWP in the treatment of RA by adjusting metabolic pathways, and the hydrophilic extract SA was superior. [Display omitted] • Salvia miltiorrhiza Bunge extracts could alleviate arthritis symptoms in CIA rats and decreased the serum levels of inflammatory factors TNF-α, IL-1β and IL-6 when combined with Tripterygium wilfordii polyglycosides. • Salvia miltiorrhiza Bunge extracts alleviated injury of liver, kidney and testis caused by Tripterygium wilfordii polyglycosides, and the hydrophilic component SA was superior. • Salvia miltiorrhiza Bunge extracts affected several metabolic pathways including linoleic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and steroid biosynthesis metabolism. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify the metabolites of rotundic acid after oral administration to rats and compare the similarities with its biotransformation by Syncephalastrum racemosum AS 3.264 using ultra-high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry. A total of fourteen metabolites were determined based on the mass spectrometry and chromatographic behaviors, among which eleven (M1–M3, M7–M14) and six (M2, M4–M8) metabolites were identified in rats and S. racemosum , respectively. Three identical metabolites (M2, M7 and M8) were found in rats and S. racemosum , indicating that there were metabolic similarities. Moreover, to confirm the results of mass spectrometry, three (M2, M4 and M7) metabolites were obtained by the means of amplifying incubation and their structures were determined by various spectroscopic analyses, and M4 was proved to be a previously undescribed compound. This results showed that in vitro assisted preparation by microbial transformation is a feasible and effective method of obtaining metabolites which are in low amounts and difficult to be prepared in vivo . [ABSTRACT FROM AUTHOR]

Five previously undescribed terpenoids (cracrosons D-H), including three clerodane diterpenoids, together with 16 known diterpenoids were isolated from Croton crassifolius (Euphorbiaceae). Cracroson D features a previously undescribed carbon skeleton with an unprecedented cyclobutane ring. Their structures, including their absolute configurations, were elucidated using spectroscopic and single-crystal X-ray diffraction analyses along with CD calculations. A plausible biogenetic pathway for cracroson D is also proposed, which was supported by the experimental results. Additionally, all of the compounds were evaluated in vitro for cytotoxicity against T24 and A549 cells using the CCK-8 method. [ABSTRACT FROM AUTHOR]

Tripterygium wilfordii polyglycoside tablet (TWP), a traditional Chinese medicine preparation, has multiple pharmacological properties, including anti-inflammatory, immune-modulatory and anti-proliferative activities. However, the reproductive toxicity of TWP greatly limits its clinical application and the mechanism of TWP-induced reproductive toxicity is not fully understood yet. This study was designed to explore the mechanism of TWP-induced testis injury in male rats. The mechanism underlying TWP-induced rat testicular injury was firstly investigated by integration of metabolomics and transcriptomics. Meanwhile, histopathological analysis, Western blot and RT-qPCR were performed to confirm the damaging effects and mechanisms of TWP on rat testis. Histopathological analysis revealed that TWP had significant testicular damage, which severely reduced the testis's tubular diameter and epithelium height. Further, TWP caused the protein level of ZO-1, CLDN11, PLZF, and OCT4 significantly downregulate, suggesting the blood-testis barrier function and spermatogenesis were damaged. Differentially expressed genes (DEGs), including 4952 upregulated and 2626 downregulated, were found in TWP-exposed testis compared to the normal group. Moreover, 77 changed metabolites were identified from testis samples. With integrated analysis of DEGs and changed metabolites, we found that glutathione metabolism and ferroptosis played an essential role in testicular injury. Additionally, the levels of ferroptosis-related protein GPX4, SLC7A11, and NRF2 were significantly downregulated, and the protein level of 4-HNE, a leading product of lipid peroxidation and oxidative stress, was upregulated. The changes in ferroptosis-related genes indicated that TWP might promote ferroptosis in rat testis. These results suggested that ferroptosis was involved in the testicular damage caused by TWP, which might provide a new strategy to alleviate TWP- induced testicular injury. [Display omitted] • TWP-induced testis injury in male rats is in dose- and time-dependent manners. • Integration of transcriptomics and metabolomics reveal the mechanism of TWP-induced testis injury. • Glutathione metabolism disorder and ferroptosis was involved in TWP-induced testicular injury. [ABSTRACT FROM AUTHOR]

Fuzi, the lateral roots of Aconitum carmichaelii Debx, plays an irreplaceable role in treating Yang deficiency and cold coagulation syndromes. However, Fuzi has a narrow margin of safety since its pharmacological constituents, Aconitum alkaloids, have potential cardiotoxicity and neurotoxicity. The current quality markers (Q-markers) for the control of Fuzi's efficacy and toxicity are 3 monoester-diterpenoid alkaloids, namely, benzoylaconine (BAC), benzoylhypaconine and benzoylmesaconine (BMA) and 3 diester-diterpenoid alkaloids, namely, aconitine (AC), hypaconitine and mesaconitine (MA). However, mounting evidence indicates that the current 6 Q-markers may not be efficacy- or toxicity-specific enough for Fuzi. The aim of this study was to explore and evaluate efficacy- or toxicity-specific potential quality markers (PQ-markers) of Fuzi. PQ-markers were explored by analyzing 30 medicinal samples and alkaloids exposed in mouse. Pharmacokinetics of PQ-markers on C57BL/6J mice were determined. Anti-inflammatory effects of PQ-markers were evaluated by λ-carrageenan-induced paw edema model and lipopolysaccharide-induced RAW264.7 cell inflammatory model, while analgesic effects were assessed by acetic acid-induced pain model and Hargreaves test. Cardiotoxicity and neurotoxicity of PQ-markers were assessed by histological and biochemical analyses, while acute toxicity was evaluated by modified Kirschner method. After in vitro and in vivo explorations, 7 PQ-markers, namely, neoline (NE), fuziline (FE), songorine (SE), 10-OH mesaconitine (10-OH MA), talatizamine, isotalatizidine and 16β-OH cardiopetalline, were found. In the herbal medicines, NE, FE, SE and 10-OH MA were found in greater abundance than many other alkaloids. Specifically, the amounts of NE, FE and SE in the Fuzi samples were all far higher than that of BAC, and the contents of 10-OH MA in 56.67% of the samples were higher than that of AC. In mouse plasma and tissues, NE, FE, SE, talatizamine, isotalatizidine and 16β-OH cardiopetalline had higher contents than the other alkaloids, including the 6 current Q-markers. The pharmacokinetics, efficacy and toxicity of NE, FE, SE and 10-OH MA were further evaluated. The average oral bioavailabilities of NE (63.82%), FE (18.14%) and SE (49.51%) were higher than that of BMA (3.05%). Additionally, NE, FE and SE produced dose-dependent anti-inflammatory and analgesic effects, and their actions were greater than those of BMA. Concurrently, the toxicities of NE, FE and SE were lower than those of BMA, since no cardiotoxicity or neurotoxicity was found in mice after NE, FE and SE treatment, while BMA treatment notably increased the creatine kinase activity and matrix metalloproteinase 9 level in mice. The average oral bioavailability of 10-OH MA (7.02%) was higher than that of MA (1.88%). The median lethal dose (LD 50) of 10-OH MA in mice (0.11 mg/kg) after intravenous injection was close to that of MA (0.13 mg/kg). Moreover, 10-OH MA produced significant cardiotoxicity and neurotoxicity, and notable anti-inflammatory and analgesic effects that were comparable to those of MA. Seven PQ-markers of Fuzi were found after in vitro and in vivo explorations. Among them, NE, FE and SE were found to be more efficacy-specific than BMA, and 10-OH MA was as toxicity-specific as MA. [Display omitted] • Seven PQ-markers of Fuzi were identified after in vitro and in vivo explorations. • NE, FE and SE were further evaluated to be more efficacy-specific than BMA. • 10-OH MA was further evaluated to be as toxicity-specific as MA. [ABSTRACT FROM AUTHOR]

Callicarpa rubella is a characteristic folk herb in the genus Callicarpa, and has abundant ethnobotanical usage as indigenous medicine in Lingnan area of P. R. China. However, the phytochemical and pharmacological properties of C. rubella was rarely investigated. Now, three new diterpenoids, named rubellapene A–C (1 – 3), along with five known analogues (4 – 8), were isolated from C. rubella. Their structures were determined by spectroscopic methods, quantum chemical electronic circular dichroism calculations and single-crystal X-ray diffraction analysis. Notably, the norditerpenoids C 18 of clerodane type (rubellapene B) was rarely found in the genus Callicarpa. The liver protective effects of all of the isolates (1 – 8) were evaluated by the changes of cell viability and transaminase content of AST and ALT in H 2 O 2 -induced BRL cells. Compound 1 , 3 – 8 exhibited that potent liver protective effects at different levels. [Display omitted] • Three new diterpenoids, rubellapene A–C (1-3), were isolated from the leaves and twigs of Callicarpa rubella. • The norditerpenoids C 18 of clerodane type (rubellapene B) was rarely found in the genus Callicarpa. • Rubellapene A exhibited that potent liver protective effects in H 2 O 2 -induced BRL cells. [ABSTRACT FROM AUTHOR]

Various traditional Chinese medicines from the genus Ilex (Aquifoliaceae) have been reported to have excellent hypolipidaemic effects. Although triterpenoids have been found to be the main active components, the underlying mechanisms have not been clarified. This study aimed to investigate the lipid-lowering effect, structure-activity relationship and action mechanism of triterpenoids from the genus Ilex. FFA was used to induce HepG2 cells to establish a classical lipid-lowering activity screening model for the activities of 31 triterpenoids, and the contents of intracellular lipids, TC, and TG were measured. Furthermore, the structure-activity relationship was discussed. Mechanistically, UPLC-Q/TOF-MS-based metabolomics and lipidomics studies were performed, and metabolic pathways were analysed to investigate the lipid-lowering mechanism. Moreover, western blotting was performed to analyse the expression of key proteins of lipid metabolism and predict the targets of action. Thirteen triterpenoids significantly reduced intracellular lipid accumulation and decreased the levels of TG and TC. Among them, rotundic acid (RA) showed stronger lipid-lowering activity than the simvastatin-positive group, and structure-activity relationship analysis indicated that the hydroxyl groups at C-3 and C-19, hydroxymethyl groups at C-23, and carboxyl groups at C-28 may be the key groups for biological activity. Twenty-two metabolites in the metabolomics study and 19 metabolites in the lipidomics study were identified. The identified biomarkers were primarily glycerophosphocholine, LysoPCs, PCs, TAGs, LysoPEs, LysoPIs and sphingolipids, which are involved in glycerophospholipid and sphingolipid metabolism. Moreover, western blotting analysis showed that the expression of SREBP-1 and HMGCR decreased, while AMPK and ACC phosphorylation and the expression of CPT1A and CYP7A1 increased in the RA-treated group. The results suggested that triterpenoids from the genus Ilex showed significant lipid-lowering effects and that RA may be a novel hypolipidaemic drug candidate. Moreover, the underlying mechanism indicated that RA showed a lipid-lowering effect by regulating glycerophospholipid and sphingolipid metabolism and activating the AMPK pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Two new clerodane diterpenoids ( 1–2 ), one new clerodane diterpenoid alkaloid ( 3 ), as well as thirteen known compounds were isolated from Croton crassifolius. The structures of new compounds were established by a combination of spectroscopic methods, including HRMS, 1 H NMR, 13 C NMR, 1 H 1 H COSY, HSQC, HMBC, NOESY and X-ray crystallographic analysis. Compound 3 is firstly reported as the clerodane-type diterpenoid alkaloid in natural products. All of the compounds were evaluated for in vitro cytotoxic activities against CT26.WT cell using the MTT method. [ABSTRACT FROM AUTHOR]

Five undescribed diterpenoids, including two ent-cleistanthane-type diterpenoids aconicleistanthanes A and B, a hetisine-type diterpenoid aconihetisine A, two aconitines-type diterpenoids aconicarmines A and B, and thirteen known diterpenoids alkaloids, were co-isolated from the lateral root of the Aconitum carmichaelii Debeaux (Ranunculaceae). Their structures were elucidated based on spectroscopic methods, and the absolute configurations were determined by X-ray diffraction and electronic circular dichroism (ECD) calculations. Among them, aconicleistanthanes A and B as ent-cleistanthane-type diterpenoid featuring a unique five-membered lactone D ring, is the first reported example of ent-cleistanthane-type diterpenoids in the Aconitum , which provided a new type of diterpene metabolites for Aconitum and enriched the chemical space of the plant of the Aconitum. In the bioassays, aconicleistanthane A significantly suppressed the production of pro-inflammatory mediators (IL-6, IL-1β and COX-2) and the protein expression of the enzyme iNOS at the concentration of 6.25 μM. [Display omitted] • Five undescribed diterpenoids were isolated from the A. carmichaelii. • Aconicleistanthanes A and B featured a unique five-membered lactone D ring. • Aconicleistanthane A exhibited good anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Ilex rotunda Thunb. (I. rotunda) is an Ilex species of Aquifoliaceae, widely distributed in East Asia. Its dried bark is commonly used as a medicinal part in the field of traditional Chinese medicine (TCM), named Ilicis Rotundae Cortex. This medicinal plant is commonly used for clearing heat and removing toxin, draining dampness and relieving pain in TCM to treat tonsillitis, acute gastroenteritis, gastric and duodenal ulcer, rheumatism, traumatic injury, and so on. It also has significant development value on lipid-lowering, hepatoprotection and anti-inflammation, but the potential mechanism needs to be further explored. More and more medicinal substances are being discovered in I. rotunda with multiple biological activities, which help to advance the ethno-pharmacological research in I. rotunda. However, to date there is a lack of a systematic summary of research progress on I. rotunda. This review aims to provide a critical summary of the current studies on I. rotunda. The progress in research on botany, phytochemistry, traditional uses, pharmacology, toxicology, quality control and pharmacokinetics of the plant is discussed. It hopes to provide useful references and guidance for the future directions of research on I. rotunda. Studies of I. rotunda were collected via Google Scholar and Baidu Scholar, PubMed, ScienceDirect, SciFinder, Web of Science, China National Knowledge Infrastructure (CNKI), WANFANG DATA and libraries. Some local books, official websites, PhD or MS's dissertations were also included. The literature cited in this review covered the period from 1956 to January 2022. Analysis of the literature indicates that I. rotunda is a potentially valuable herbal medicine for the therapeutic of various diseases. To date, 120 compounds were found and identified in I. rotunda , mainly including triterpenoids, phenylpropanoids, etc. Modern pharmacological studies also found that the plant has the activities of protecting the cardiovascular system, lowering lipids and protecting the liver, as well as being an anti-inflammatory, anti-tumor and antibacterial. This review summarizes the results from current studies of I. rotunda. However, the current explanation seems insufficient and unsatisfactory, in terms of the relationships between the traditional uses and the modern pharmacological activities, the mechanisms and the material basis. Thus, a critical and comprehensive evaluation is necessary to explore its future research prospects and development direction. [Display omitted] • The highlights of the paper are: • Anti-inflammatory and TCM efficacy are linked in Ilicis Rotundae Cortex (IRC). • Anti-lipid metabolism disorders and TCM efficacy are linked in IRC. • Rotundic acid, pedunculoside and syringin could be key medicinal substances. • This is the first systematic critical review of studies on Ilex rotunda Thunb. [ABSTRACT FROM AUTHOR]

Hypericum sampsonii Hance (Yuanbaocao), a traditional herbal medicine with various pharmacological properties, is traditionally used to treat diarrhea and enteritis in China for hundreds of years. Investigations have uncovered its anti-inflammatory effects and corresponding bioactive constituents in H. sampsonii , however, the mechanisms of action for the treatment of enteritis are still unclear. This study aims to investigate the therapeutic effects and molecular mechanisms of H. sampsonii in a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model. The major ingredients of the ethyl acetate extract (HS) in H. sampsonii were analyzed by UPLC-QTOF-MS. The inflammatory state of UC mice was caused by 3% DSS once daily for seven days. During DSS treatment, the mice in the positive drug group and the other three groups were orally administered 5-ASA (positive control) or HS daily. After treatment with HS or 5-ASA for a week, colonic pathological observation and the molecular biological index were performed for therapeutic evaluation, including visual inspection in the length and weight of colons and spleens, pathological morphology by hematoxylin and eosin (HE) staining, determination of oxidative markers, inflammatory cytokines and tumor necrosis factor-alpha (TNF-α) levels in colonic tissues as well as spleen index. Gene expression levels of inflammatory cytokines, antioxidant enzymes and PDE4 were detected using kits and PCR, while the expression of colonic tight junction proteins and relative signals of PKA/CREB signaling pathway were analyzed by Western blot. The main components in HS were found to be polycyclic polyprenylated acylphloroglucinols (PPAPs). HS distinctly alleviated DSS-stimulated UC-like lesions symptoms as evidenced by a significant recovery from body weight, colon lengths, and histological injuries of colons. HS reduced the accumulation of pro-inflammatory cytokines and improved the mRNA level of IL-10. Simultaneously, the colonic mRNA expression levels of IL-1β, IL-17, iNOS and COX-2 were all significantly suppressed by HS in a dose-dependent manner. Furthermore, HS restored the protein expression of tight junction-associated protein (ZO-1 and occluding). Besides, HS significantly inhibited the protein level of PDE4 and decreased the expressions of PKA and phosphorylated CREB. This is the first work about main composition and anti-UC effect of Hypericum sampsonii Hance. For the first time, this study reveals HS is not toxic in a single dose and exert significantly protective effect in DSS-colitis mice. The underlying mechanisms may involve the improvement to inflammatory status, the protection for intestinal barrier function, the inhibition of PDE4, and the activation of PKA/CREB signaling pathway. This study provided an experimental basis for the traditional application of H. sampsonii Hance in the treatment of diarrhea and dysentery. [Display omitted] • List of highlights. • Polycyclic polyprenylated acylphloroglucinols were the main composition of Hypericum sampsonii. • Hypericum sampsonii exert significantly protective effect in DSS-colitis mice. • The underlying mechanisms may involve PDE4/PKA/CREB signaling pathway. [ABSTRACT FROM AUTHOR]