This study aims to elucidate the chemical composition of the dichloromethane extract from the aerial parts of Ferula ferulaeoides (DEAFF) and to explore its biological activities. The composition of DEAFF was analyzed by UHPLC-Q-Orbitrap-MS/MS. Then, the carrageenan-induced tail thrombosis model, xylene-induced ear swelling model, and acetic acid-induced writhing model were established to evaluate the relevant activities of DEAFF. Network pharmacology research and molecular docking were conducted to elucidate the pathways and key targets underlying the multiple activities of DEAFF. A total of 30 chemical constituents were tentatively identified in DEAFF based on UHPLC-Q-Orbitrap-MS/MS analysis. Pharmacodynamic results showed that DEAFF significantly reduced the proportion of thrombus in the tail of mice, effectively alleviated ear swelling, improved the degree of ear tissue lesions, and significantly reduced the number of writhing movements in mice, indicating that it has multiple pharmacological effects such as antithrombosis, anti-inflammation, and analgesia. Network pharmacology studies have shown that multiple pathways such as the PI3K-Akt signaling pathway and the MAPK signaling pathway play a crucial role in the pharmacological effects of DEAFF. In this study, the chemical components of DEAFF were preliminarily identified, and its effects on thrombosis prevention, anti-inflammation, and analgesia were systematically investigated.

Ethnopharmacological relevance: Myristica fragrans (Nutmeg) is a commonly used Chinese herbal medicine and edible spice. According to Pharmacopoeia of People's Republic of China, it has the effects of warming the middle and promoting qi, astringent intestines, and antidiarrheal. In the record of Compendium of Materia Medica, it is the myristica fragrans water extract (MFWE) that is utilized for therapeutic purposes of gastrointestinal disorders frequently. Research purpose: This study is to investigate the pharmacodynamic material foundation and molecular mechanism of myristica fragrans on gastric ulcers using UHPLC-Q-Orbitrap-MS/MS with network pharmacology and experimental verification. This may provide theoretical guidance for the clinical use of myristica fragrans, and support a theoretical foundation for its future advancement into natural functional products that can relieve acute gastric ulcers. Materials and methods: Using UHPLC/MS technology and network pharmacology, we identified possible active chemicals molecules, screened out core targets and core pathways, and simulated drug target binding through molecular docking situations. Acute gastric ulcer was caused by intragastric administration of absolute ethanol (0.075 ml/10g). Myristica fragrans water extract (182 mg/kg and 364 mg/kg) was administered orally 14 days in advance. The same method was used to distribute 0.5% carboxymethyl cellulose solution into the Model and Control group. The mice were murdered on the 15th day. Following the sacrifice, the gastric tissue was removed for histological analysis. The tissue needs to detect levels of IL-1 beta, TNF-alpha, IL-10, and IL-6 as well as the activity of SOD, GSH-Px, MDA, and MPO. In addition, H&E staining and the TUNEL method were used to observe the effect on the gastric mucosa of mice. Western blot was used to detect apoptosis, ferroptosis, and antioxidation-related proteins.

Allium chinense G. Don is valued for its edible and medicinal qualities. It has been reported that Allium chinense has the potential to inhibit platelet activation, but its mechanism of action is unknown, which needs to be further explored. This study investigates the anti-myocardial ischemia–reperfusion (I/R) injury potential of Allium chinense from the perspective of platelet activation, focusing on its chemical composition and underlying mechanisms of action. A combination of transcriptome sequencing, molecular docking, and experimental validation was employed in our study. The antiplatelet active fraction MT-95ET of Allium chinense was screened by the ADP-induced platelet aggregation model in vitro. In vivo experiments demonstrated that MT-95ET can reduce the myocardial injury of I/R rats and inhibit I/R-induced platelet activation, adhesion, and aggregation. UHPLC-Q-Orbitrap-MS/MS was used to identify 13 compounds from MT-95ET. Transcriptome sequencing and molecular docking identified aerobic glycolysis key checkpoints PDK1 and PKM2 as key targets, with Sarsasapogenin and Hecogenin exhibiting strong binding affinities to these proteins. Western blot analysis further validated that MT-95ET downregulated PKM2 and PDK1, indicating a possible mechanism for its antiplatelet effects and anti-myocardial I/R injury.

Siraitia grosvenorii Swingle is one of the first approved medicine food homology species in China, and it has been used as a natural sweetener in the food industry and as a traditional medicine to relieve cough and reduce phlegm. However, many S. grosvenorii roots are discarded yearly, which results in a great waste of resources. Twelve undescribed norcucurbitacin-type triterpenoid glycosides, siraitiaosides A-L (1-12), and six known analogs (13-18) were isolated from the roots of S. grosvenorii. The structures of isolated norcucurbitacin glycosides were elucidated by comprehensive data analyses, including HRESIMS, UV, IR, NMR, ECD calculations, and X-ray crystallography analysis. Siraitiaosides A-E (1-5) featured an unusual 19,29-norcucurbitacin framework while siraitiaosides F-L (6-12) featured a rare 29-norcucurbitacin framework. Notably, compound 4 displayed moderate anti-acetylcholinesterase (AChE) activity with an IC50 of 21.0 μM, meanwhile, compounds 16 and 18 exhibited pronounced cytotoxic activities against MCF-7, CNE-1, and HeLa cancer cell lines with IC50 values of 2.1-15.2 μM. In silico studies showed that compound 4 bound closely to AChE with a binding energy of -5.04 kcal/mol, and compound 18 could tightly bind to PI3K, AKT1, ERK2, and MMP9 proteins that related to autophagy, apoptosis, migration/invasion, and growth/proliferation. In summary, the roots of Siraitia grosvenorii have potential medicinal values due to the multiple bioactive components.

Ferula is a genus of flowering plants known for its edible and medicinal properties. Since ancient times, many species of Ferula have been used in traditional medicine to treat various health issues across countries, such as digestive disorders, respiratory problems, and even as a remedy for headaches and toothaches. In addition, they are also used as a flavoring agent in various cuisines. As the main active ingredients in Ferula, sesquiterpenes and their derivatives, especially sesquiterpene coumarins, sesquiterpene phenylpropanoids, and sesquiterpene chromones, have attracted the attention of scientists due to the diversity of their chemical structures, as well as their extensive and promising biological properties, such as antioxidative, anti-inflammatory, antibacterial properties. However, there has not been a comprehensive review of sesquiterpenes and their derivatives from this plant. This review aims to provide an overview of the chemical structures, biosynthetic pathways, and biological properties of sesquiterpenes and sesquiterpene derivatives from Ferula, which may help guide future research directions and possible application methods for this valuable edible and medicinal plant.

Allium is a common functional vegetable with edible and medicinal value. Allium plants have a special spicy taste, so they are often used as food and seasoning in people’s diets. As a functional food, Allium also has abundant biological activities, some of which are used as drugs to treat diseases. By consuming Allium on a daily basis, people can receive active compounds of natural origin, thereby improving their health status and reducing the likelihood of disease. Steroidal saponins are important secondary metabolites of Allium, which are formed by the steroidal aglycone group and sugar. Steroidal saponins have various physiological activities, such as hypoglycemic, antiplatelet aggregation, anti-inflammatory, antitumor, antimicrobial, and enzyme activity inhibition, which is one of the key reasons why Allium has such significant health benefits. The structural diversity and rich biological activities of steroidal saponins make Allium important plants for both food and medicine. In this paper, the chemical structures, biological activities, and structure–activity relationships of steroidal saponins isolated from Allium are reviewed, and the biosynthetic pathways of some key compounds are proposed as well, to provide a molecular reference basis based on secondary metabolites for the health value of Allium.

Eight undescribed sesquiterpene coumarins (1-8) and twenty known ones (9-28), were isolated from the aerial parts of Ferula sinkiangensis K. M. Shen. Their structures were elucidated based on the comprehensive analysis of UV, IR, HRESIMS, 1D, and 2D NMR data. The absolute configuration of 1 was determined by single crystal X-Ray diffraction, while the absolute configurations of 2-8 were determined by comparisons of experimental and calculated electrostatic circular dichroism spectra. Compound 2 is the first hydroperoxy sesquiterpene coumarin from the genus Ferula, while compound 8 has an unusual 5',8'-peroxo bridge. Griess reaction results indicated compound 18 significantly decreased nitric oxide production of the lipopolysaccharide-stimulated RAW 264.7 macrophages with an IC50 value of 2.3 μM, and ELISA results revealed that compound 18 effectively inhibited tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 expressions.

葫芦烷型降三萜类化合物是一类结构新颖的化合物,是在葫芦烷型三萜的30个碳骨架的基础上减少1个或几个碳所得.按其缺少碳原子的位置可分为2-降(a)、3-降(b)、19-降(c)、27-降(d)、29-降(e)、19,29-降(f)、25,26,27-降(g)、24,25,26,27-降(h)、23,24,25,26,27-降(i)、22,23,24,25,26,27-降(j)、22,23,24,25,26,27,29-降(k)、20,21,22,23,24,25,26,27-降(1)共12种类型.此类化合物结构新颖多样,具有抗肿瘤、抗炎、降血糖和抗氧化等多种药理活性.对葫芦烷型降三萜类化合物的植物分布、化学结构特征以及药理活性进行系统的总结,以期为该类化合物进一步的开发与合理利用提供参考.

目的:研究新疆阿魏Ferula sinkiangensis K.M.Shen地上部位的化学成分,以发现新的抗炎活性先导化合物.方法:采用硅胶、Sephadex LH-20凝胶、半制备液相等色谱方法对新疆阿魏地上部位的二氯甲烷部位进行分离纯化,通过紫外光谱、红外光谱、高分辨质谱、核磁共振波谱、圆二色散谱和Mosher反应等对化合物结构进行鉴定,并对其体外抗炎活性进行筛选.结果:从新疆阿魏地上部位95％乙醇提取物的二氯甲烷部位分离得到1对新的非对映异构体(4'R,5'S,6'R,9'R)-新疆阿魏醇A(1)和(4'S,5'R,6'R,9'R)-新疆阿魏醇A(2),其对脂多糖诱导的小鼠单核巨噬细胞RAW264.7产生一氧化氮具有不同程度的抑制作用.结论:化合物1和2为从新疆阿魏地上部位中分离得到的1对新的非对映异构体且具有一定的抗炎活性.

目的:采用可同时测定32个吡咯里西啶类生物碱(PAs)的液相色谱串联质谱法(LC-MS/MS)对紫草药材及含款冬花和紫草的中成药制剂中的PAs成分进行鉴定和含量分析.方法:药材和中成药制剂经提取后用阳离子交换固相萃取小柱净化富集;富集后的样品采用Phenomenex Prodigy 5μODS3100A色谱柱(150 mm×3.2 mm,5μm)梯度洗脱后,使用电喷雾离子源、正离子多反应监测模式进行检测.结果:14种含款冬花的中成药制剂所含PAs主要为克氏千里光碱,PAs的总检出量为0.059～5.330μg·g-1或μg·mL-1,按药品说明书计算的PAs日摄入量为2.24～95.92μg;紫草药材主要含有蓝蓟定、石松胺、印美定及其氮氧化物等PAs,8批药材的PAs总检出量为0.60～140.69μg·g-1;在10种含紫草的中成药制剂中,PAs日摄入量为0.38～25.20μg.结论:大多数紫草药材PAs含量相对较低,有望通过控制紫草药材中PAs含量,使含紫草的中成药制剂中PAs含量满足欧盟限量要求;而对于含款冬花的中成药制剂中,大多数(8/14)PAs检出量超过了欧盟限量的10倍,提示含款冬花的中成药制剂有必要开展克氏千里光碱的质量控制及其摄入所致的潜在安全风险评价.

Gastric cancer is considered to be one of the most common causes of cancer death worldwide due to its high recurrence and metastasis rates. The molecule 23,24-Dihydrocucurbitacin E (DHCE) is a cucurbitacin-derived tetracyclic triterpenoid compound that has anti-tumor activity, but the exact mechanism remains to be elucidated. This research aimed to explore the effects of DHCE on human gastric cancer cells and the possible mechanisms. The results showed that DHCE suppressed proliferation, migration, and invasion of gastric cancer cells, as well as induced apoptosis and G2/M phase arrest. Mechanistically, the potential targets and pathways of DHCE were predicted using database screening and verified using a molecular docking study, fluorescence staining, and Western blot. The results indicated that DHCE obviously inhibited the kinase activity of ERK2 via targeting its ATP-binding domain, destroyed F-actin microfilament, and reduced the expression levels of Ras, p-c-Raf, ERK, p-ERK, and MMP9 proteins. Collectively, our study demonstrated that DHCE suppressed gastric cancer cells' proliferation, migration, and invasion through targeting ERK2 and disrupting the Ras/Raf/ERK/MMP9 signaling pathway. These properties make DHCE a promising candidate drug for the further design and development of novel and effective Ras/Raf/ERK/MMP9 pathway inhibitors for treating gastric cancer.

Four novel triterpenoid alkaloids, siragrosvenins A–D (1–4), and two new cucurbitane-type triterpenoids, siragrosvenins E–F (5, 6), together with eight known analogs (7−14), were isolated from the roots of Siraitia grosvenorii. Compounds 1−4 possessed a rare cucurbitane-type triterpenoid scaffold, featuring an extra pyrazine unit via the Strecker reaction in the cucurbitane framework. Compound 5 displayed a 6/6/6/5/6/5-fused polycyclic ring system, with an uncommon fused furan and pyran ring in the side chain. All the structures were characterized by extensive spectroscopic analysis, including HRESIMS, NMR, and X-ray crystallographic data. It is worth noting that the DP4+ analysis method was applied for the first time to determine the absolute configurations of the trihydroxybutyl moiety in the side chain of compounds 1–4. In vitro cytotoxicity screening found that compounds 4, 8, 9, 13, and 14 exhibited remarkable cytotoxic activities against three cell lines with IC50 values ranging from 1.44 to 9.99 μM. Siragrosvenin D shows remarkable cytotoxic activity on MCF-7 cells. As a result, it inhibited the proliferation of MCF-7 cells and reduced their viability via the induction of G2/M phase arrest and significantly induced apoptosis in MCF-7 cells.

A new alkaloid featured with a dibenz[c,e]azepin-5-one scaffold, namely emililactam A (3), together with a known pyrrolidine alkaloid (emilisonchine, 1) and a known flavonoid alkaloid [8-(2″-pyrrolidinone-5″-yl)-quercetin, 2] were isolated from the aerial parts of Emilia sonchifolia. Compounds 1 and 2 were isolated as racemic forms which were further separated, for the first time, to their corresponding enantiomers [(+)-1/(-)-1 and (+)-2/(-)-2], respectively, by using chiral-phase HPLC. The structure of new compound 3 was elucidated by extensive spectroscopic analysis. In addition, the absolute configurations of optically pure (+)-1/(-)-1 and (+)-2/(-)-2 were determined by the time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculations. In an in vitro bioassay, compounds (+)-1, (-)-1, (±)-1, and 3 exhibited moderate neuroprotective effects against corticosterone-induced injuries of PC12 cells.

Four undescribed sulfoxide-containing derivatives, sinkiangenoxides A and B, (2 Z , 4 E )-sinkiangenoxide C, and (2 E , 4 E )-sinkiangenoxide C ( 1 - 4 ), and one known compound, 1-(methylthio)propyl ( E )-1-propenyl disulfide ( 5 ), were isolated from the resin of Ferula sinkiangensis . Their structures were determined based on spectroscopic methods, including IR, UV, HRESIMS, NMR, and CD analysis. Compounds 2 - 4 showed moderate cytotoxic activities against four human cancer cell lines with IC (50) values ranging from 15.0 to 40.3 mu M. Sinkiangenoxide B ( 2 ) was shown to induce apoptosis in HepG2 cells. In addition, compound 5 effectively attenuated lipopolysaccharide-induced nitric oxide release and TNF- alpha , IL-1 beta , IL-6, and IL-10 expression.

This study was to analyze the pyrrolizidine alkaloids (PAs) in Eupatorium fortunei herbs and its derived finished products with a view to evaluating their effects on the proliferation and oligodendrogenesis of neural progenitor cells (NPCs). Using a LC-MS/MS method with 32 PAs reference standards, 8 PAs including intermedine, intermedine N-oxide, lycopsamine, lycopsamine N-oxide, retronecine, seneciphylline and senkirkine and 7-acetylintermedine N-oxide were identified with intermedine N-oxide and lycopsamine N-oxide being most abundant. The total PA amounts were found to vary from 0.18 to 61.81 μg/g in 30 batches of herbs and from 0.86 to 36.96 μg/g in 4 commercial finished products, respectively. Risk assessments indicated that the short-term intake seemed unlikely lead to acute toxic effects but the chronic use warranted cautions. Using NPCs derived from mouse induced pluripotent stem cells as an in vitro testing model, intermedine, intermedine N-oxide and lycopsamine N-oxide appeared to decrease cell viability at 30 μM whereas intermedine N-oxide inhibited oligodendrogenesis of NPCs at 10 μM. The present results suggested that the PAs in the majority of E. fortunei herbs and the derived products not only resulted in their exposure far exceeding the acceptable intake limit (i. e. 1.0 μg PA per day for adults) in herbal medicinal products recommended by the European Medicines Agency but also induced neurotoxicity to NPCs in vitro.

Pyrrolizidine alkaloids (PAs) are a class of natural toxins with hepatotoxicity, genotoxicity and carcinogenicity. They are endogenous and adulterated toxic components widely found in food and herbal products. In this study, a sensitive and efficient ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was used to detect the PAs in 386 kinds of Chinese herbal medicines recorded in the Chinese Pharmacopoeia (2020). The estimated daily intake (EDI) of 0.007 μg/kg body weight (bw)/day was adopted as the safety baseline. The margin of exposure (MOE) approach was applied to evaluate the chronic exposure risk for the genotoxic and carcinogenic potential of PAs. Results showed that PAs was detected in 271 out of 386 samples with a content of 0.1–25,567.4 μg/kg, and there were 20 samples with EDI values above the baseline, 0.007 μg/kg bw/day. Beyond that, the MOE values for 10 out of 271 positive samples were below 10,000. Considering the actual situation, Haber’s rule was used to assume two weeks exposure every year during lifetime, and still the MOE values for four out of 271 positive samples were under 10,000, indicating these products may have potential health risk. The developed method was successfully applied to detect the PAs-containing Chinese herbal medicines. This study provides convincing data that can support risk management actions in China and a meaningful reference for the rational and safe use of Chinese herbal medicines.

Porcine deltacoronavirus (PDCoV) is a newly discovered swine enteropathogenic coronavirus with worldwide distribution. However, efficient strategies to prevent or treat the infection remain elusive. Our in vitro study revealed that ergosterol peroxide (EP) from the mushroom Cryptoporus volvatus has efficient anti-PDCoV properties. The aim of this study is to evaluate the potential of EP as a treatment for PDCoV in vivo and elucidate the possible mechanisms. Seven-day-old piglets were infected with PDCoV by oral administration in the presence or absence of EP. Piglets infected with PDCoV were most affected, whereas administration of EP reduced diarrhea incidence, alleviated intestinal lesion, and decreased viral load in feces and tissues. EP reduced PDCoV-induced apoptosis and enhanced tight junction protein expressions in the small intestine, maintaining the integrity of the intestinal barrier. EP showed immunomodulatory effect by suppressing PDCoV-induced pro-inflammatory cytokines and the activation of IκBα and NF-κB p65, and upregulating IFN-I expression. Knockdown of p38 inhibited PDCoV replication and alleviated PDCoV-induced apoptosis, implying that EP inhibited PDCoV replication and alleviated PDCoV-induced apoptosis via p38/MAPK signaling pathway. Collectively, ergosterol peroxide can protect piglets from PDCoV, revealing the potential of EP for development as a promising strategy for treating and controlling the infection of PDCoV.

The gut epithelium is a mechanical barrier that protects the host from the luminal microenvironment and interacts with the gut microflora, which influences the development and progression of ulcerative colitis (UC). Licochalcone A (LA) exerts anti-inflammatory effects against UC; however, whether it also regulates both the gut barrier and microbiota during colitis is unknown. The current study was conducted to reveal the regulatory effects of LA on the intestinal epithelium and gut microflora in C57BL/6 mice subjected to dextran sodium sulfate (DSS). Sulfasalazine (SASP) was used as the positive control. Results of clinical symptoms evaluation, hematoxylin, and eosin (H&E) staining, and enzyme-linked immunosorbent (ELISA) assays showed that LA significantly inhibited DSS-induced weight loss, disease activity index (DAI) increase, histological damage, and gut inflammation. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemical (IHC) analysis showed that LA maintained the integrity of the intestinal barrier by suppressing cell apoptosis and preserving the expression of tight junction (TJ) proteins. Notably, the optimal dose of LA for gut barrier preservation was low, while that for anti-inflammatory effects was high, indicating that LA might preserve gut barrier integrity via direct effects on the epithelial cells (ECs) and TJ proteins. Furthermore, 16S rRNA analysis suggested that the regulatory effect of LA on the gut microbiota differed distinctly according to dose. Correlation analysis indicated that a low dose of LA significantly modulated the intestinal barrier-associated bacteria as compared with a moderate or high dose of LA. Western blot (WB) analysis indicated that LA exhibited anti-UC activity partly by blocking the mitogen-activated protein kinase (MAPK) pathway. Our results further elucidate the pharmacological activity of LA against UC and will provide valuable information for future studies regarding on the regulatory effects of LA on enteric diseases.