Nine new nor-3,4-seco-dammarane triterpenoids from the leaves of Cyclocarya paliurus and their hypoglycemic activity.

This manuscript describes the isolation of nine new nor-3,4-seco-dammarane triterpenoids, norqingqianliusus A-I (1-9) and one known nortriterpenoid (10) from Cyclocarya paliurus leaves. Norqingqianliusus A and B (1 and 2) possess a unique 3,4-seco-dammarane-type C26 tetranortriterpenoid skeleton. The compounds were structurally characterized through modern spectroscopic techniques. Moreover, the potential mechanism of hypoglycemic activity was further explored by studying the effects on glucosamine-induced insulin resistant HepG2 cells. In vitro hypoglycemic effects of all of the isolates were investigated using insulin resistant HepG2 cells. The glucose consumption was significantly promoted by compound 10, in a dose-dependent manner, thus alleviating damage in IR-HepG2 cells. Besides, it reduced the PEPCK and GSK3ß gene expression, involved in glucose metabolism. The anti-diabetic effects of the plant, utilized traditionally, can hence be attributed to the presence of nor-3,4-seco-dammarane triterpenoids in the leaves.

Safety and efficacy of thermo-expandable metallic stent in ureteral stricture following gynecological malignancy surgery and radiotherapy: a single center experience with 33 cases.

BACKGROUND: The effectiveness of metallic stents in treating ureteral strictures following surgery and radiotherapy for gynecological tumors is currently uncertain. We aimed to investigate the efficacy and safety of thermo-expandable metallic stent (Memokath) in the treatment of ureteral stricture after radiotherapy for gynecological tumors. METHODS: In this descriptive cross-sectional study, 27 patients with ureteral stricture were treated with Memokath stent after gynecological tumor radiotherapy with or without chemotherapy that was admitted to our hospital from August 2021 to August 2023. Clinical data on efficacy, safety, and complications during stent insertion and indwelling were analyzed. RESULTS: The successful insertion of thirty-three stents in twenty-seven patients studied. The stenosis length was 10.14 ± 6.76 cm, and the hospitalization was 4.43 ± 1.83 days. One patient has died from the primary disease carrying a patency stent. The Kaplan-Meier graph showed that the cumilative patency rate of patients with thermo-expandable metallic stent were 92.4% (SD = 5.2%) in eight months, 77.4% (9.1%) in 12 months and 67.7% (SD = 12%) in 29 months, while the cumilative survival rate was 87.5% (SD = 11.5%) in 29 months. The stent patency was 81.48% and later complications of stent indwelling were 5/27, including refractory urinary tract infection (UTI) in three cases, stent migration, and stent intolerance respectively. The creatinine levels, hydronephrosis degree, and glomerular filtration rate improved after the operation, and the first two indicators were statistically significant. CONCLUSION: Memokath stent is a safe and effective treatment for ureteral stricture after surgery and radiotherapy with or without chemotherapy for gynecological tumors.

Qingqianliutianosides A-E: five new sweet dammarane triterpenoid glycosides derived from the leaves of Cyclocarya paliurus - identification, characterization and interactions with T1R2/T1R3 sweet taste receptors.

BACKGROUND: Cyclocarya paliurus, as a new food resource, is utilized extensively in human and animal diets due to its bioactive compounds, health benefits, and its highly prized sweet flavor. This study aimed to investigate the sweet-taste ingredient of C. paliurus leaves. RESULTS: Five new dammarane triterpenoid glycosides were isolated and identified as qingqianliutianosides A-E (1-5) by comprehensive spectroscopic data analysis and a single crystal X-ray diffraction experiment. Qingqianliutianoside A (1) and qingqianliutianoside C (3), present in relatively high quantities in the plant, were shown to exhibit sweetness by sensory evaluation and electronic tongue analysis. Further monitoring was conducted on the content changes in 3 in leaves at different growth stages, indicating that 3 reached its peak content in April and then showed a decreasing trend. Molecular docking studies revealed that T1R2/T1R3 receptors Ser212, Ser105, Thr239, Asn380, Thr305, and Val381 may play critical roles, demonstrating that hydrogen bonding and hydrophobic interactions were the dominant interaction forces between all of the identified compounds and the active sites in the Venus flytrap module of the T1R2/T1R3 receptors. CONCLUSION: Qingqianliutianosides A-E are promising natural source sugar substitutes for use in functional foods and beverages. © 2024 Society of Chemical Industry.

Chemical Constituents and α-Glucosidase Inhibitory, Antioxidant and Hepatoprotective Activities of Ampelopsis grossedentata.

Ampelopsis grossedentata is a valuable medicinal and edible plant, which is often used as a traditional tea by the Tujia people in China. A. grossedentata has numerous biological activities and is now widely used in the pharmaceutical and food industries. In this study, two new flavonoids (1-2) and seventeen known compounds (3-19) were isolated and identified from the dried stems and leaves of A. grossedentata. These isolated compounds were characterized by various spectroscopic data including mass spectrometry and nuclear magnetic resonance spectroscopy. All isolates were assessed for their α-glucosidase inhibitory, antioxidant, and hepatoprotective activities, and their structure-activity relationships were further discussed. The results indicated that compound 1 exhibited effective inhibitory activity against α-glucosidase, with an IC50 value of 0.21 µM. In addition, compounds 1-2 demonstrated not only potent antioxidant activities but also superior hepatoprotective properties. The findings of this study could serve as a reference for the development of A. grossedentata-derived products or drugs aimed at realizing their antidiabetic, antioxidant, and hepatoprotective functions.

Heilaohuacid G, a new triterpenoid from Kadsura coccinea inhibits proliferation, induces apoptosis, and ameliorates inflammation in RA-FLS and RAW 264.7 cells via suppressing NF-𝜠B pathway.

Heilaohu, the roots of Kadsura coccinea, has been used in Tujia ethnomedicine to treat rheumatic arthritis (RA). Heilaohuacid G (1), a new 3,4-seco-lanostane type triterpenoid isolated from the ethanol extract of Heilaohu, whose structure was determined using HR-ESI-MS data, NMR spectroscopic analyses, and ECD calculations. In this study, our purpose is to elucidate the mechanisms of Heilaohuacid G in the treatment of RA by inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells and inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. The biological activity screening experiments indicated that Heilaohuacid G significantly inhibited proliferation of RA-FLS cells with IC50 value of 8.16 ± 0.47 µM. CCK-8 assay, ELISA, flow cytometry assay, and Western blot were used to measure the changes of cell viability, apoptosis, and the release of inflammatory cytokines. Heilaohuacid G was found not only induced RA-FLS cell apoptosis, but also inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. Furthermore, Heilaohuacid G (p.o.) at doses of 3.0, 6.0, and 12.0 mg/kg and the ethanol extracts of Heilaohu (p.o.) at doses of 200, 400, and 800 mg/kg both were confirmed antiinflammatory effects on xylene-induced ear mice edema model.

The traditional ethnic herb Tadehagi triquetrum from China: a review of its phytochemistry and pharmacological activities.

CONTEXT: Tadehagi triquetrum (Linn.) Ohashi (Fabaceae) (TT), is a traditional herbal medicine used especially in China's ethnic-minority communities, such as the Zhuang, Dai, Li and Wa aeras. As an ethnic medicine, it has long been used to treat various diseases. OBJECTIVE: This review summarised the phytochemical and pharmacological progress on TT from 1979 to October, 2021 by highlighting its chemical classification, structural features, pharmacological applications and folk applications to provide inspirations and suggestions for accelerating further research of this traditional phytomedicine. METHODS: The information on TT in this article has been obtained using these multiple scientific databases including Scifinder, Web of Science, ScienceDirect, Wiley, ACS publications, Springer, PubMed, China Knowledge Resource Integrated Database from the China National Knowledge Infrastructure (CNKI), Google Scholar and Baidu Scholar. Some information was also collected from classic literature on traditional Chinese medicines. RESULTS: More than 70 compounds have been isolated and reported from TT to date by the comprehensive analysis of the current literature. A large number of traditional uses and pharmacological studies have exhibited diversified bioactivities of various TT extracts and its metabolites, including anti-inflammatory, antimicrobial, anti-hepatitis B virus, hepatoprotective, insecticidal, etc. CONCLUSIONS: As a famous traditional medicine with a long history, TT has various medicinal uses and some of them have been supported by modern pharmacological researches. Further detailed studies on the action mechanisms, pharmacodynamics and structure-function relationships of single compounds or active constituents from TT are also required.

Lignans from Tujia Ethnomedicine Heilaohu: Chemical Characterization and Evaluation of Their Cytotoxicity and Antioxidant Activities.

Heilaohu, the roots of Kadsura coccinea, has a long history of use in Tujia ethnomedicine for the treatment of rheumatoid arthritis and gastroenteric disorders, and a lot of work has been done in order to know the material basis of its pharmacological activities. The chemical investigation led to the isolation and characterization of three new (1⁻3) and twenty known (4⁻23) lignans. Three new heilaohulignans A-C (1⁻3) and seventeen known (4⁻20) lignans possessed dibenzocyclooctadiene skeletons. Similarly, one was a diarylbutane (21) and two were spirobenzofuranoid dibenzocyclooctadiene (22⁻23) lignans. Among the known compounds, 4⁻5, 7, 13⁻15 and 17⁻22 were isolated from this species for the first time. The structures were established, using IR, UV, MS and NMR data. The absolute configurations of the new compounds were determined by circular dichroism (CD) spectra. The isolated lignans were further evaluated for their cytotoxicity and antioxidant activities. Compound 3 demonstrated strong cytotoxic activity with an IC50 value of 9.92 µM, compounds 9 and 13 revealed weak cytotoxicity with IC50 values of 21.72 µM and 18.72 µM, respectively in the HepG-2 human liver cancer cell line. Compound 3 also showed weak cytotoxicity against the BGC-823 human gastric cancer cell line and the HCT-116 human colon cancer cell line with IC50 values of 16.75 µM and 16.59 µM, respectively. A chemiluminescence assay for antioxidant status of isolated compounds implied compounds 11 and 20, which showed weak activity with IC50 values of 25.56 µM and 21.20 µM, respectively.

Identification of potential diagnostic biomarkers of acute pancreatitis by serum metabolomic profiles.

Acute pancreatitis (AP) is defined as an acute inflammation of pancreas that may cause damage to other tissues and organs depending upon the severity of symptoms. The diagnosis of AP is usually made by detection of raised circulating pancreatic enzyme levels, but there are occasional false positive and false negative diagnoses and such tests are often normal in delayed presentations. More accurate biomarkers would help in such situations. In this study, the global metabolites' changes of AP patients (APP) were profiled by using gas chromatography-mass spectrometry (GC-MS). Multivariate pattern recognition techniques were used to establish the classification models to distinguish APP from healthy participants (HP). Some significant metabolites including 3-hydroxybutyric acid, phosphoric acid, glycerol, citric acid, d-galactose, d-mannose, d-glucose, hexadecanoic acid and serotonin were selected as potential biomarkers for helping clinical diagnosis of AP. Furthermore, the metabolite changes in APP with severe and mild symptoms were also analyzed. Based on the selected biomarkers, some relevant pathways were also identified. Our results suggested that GC-MS based serum metabolomics method can be used in the clinical diagnosis of AP by profiling potential biomarkers.

An Efficient Workflow for Quality Control Marker Screening and Metabolite Discovery in Dietary Herbs by LC-Orbitrap-MS/MS and Chemometric Methods: A Case Study of Chrysanthemum Flowers.

LC-MS is widely utilized in identifying and tracing plant-derived food varieties but quality control markers screening and accurate identification remain challenging. The adulteration and confusion of Chrysanthemum flowers highlight the need for robust quality control markers. This study established an efficient workflow by integrating UHPLC-Orbitrap-MS/MS with Compound Discoverer and chemometrics. This workflow enabled the systematic screening of 21 markers from 10,540 molecular features, which effectively discriminated Chrysanthemum flowers of different species and cultivars. The workflow incorporated targeted and untargeted methods by employing diagnostic product ions, fragmentation patterns, mzCloud, mzVault, and in-house databases to identify 206 compounds in the flowers, including 17 screened markers. This approach improved identification accuracy by reducing false positives, eliminating in-source fragmentation interference, and incorporating partial verification utilizing our established compound bank. Practically, this workflow can be instrumental in quality control, geolocation determination, and varietal tracing of Chrysanthemum flowers, offering prospective use in other plant-derived foods.

Starch nanoparticles with predictable size prepared by alternate treatments of ball milling and ultrasonication.

In this study, starch nanoparticles (SNPs) were prepared by alternate treatments of liquid nitrogen ball milling and ultrasonication. The impact, shear and friction forces produced by ball milling, and acoustic cavitation and shear effects generated by ultrasonication disrupted starch granules to prepare SNPs. The SNPs possessed narrow particle size distribution (46.91-210.52 nm) and low polydispersity index (0.28-0.45). Additionally, the SNPs exhibited the irregular fragments with good uniformity. The relative crystallinity decreased from 34.91 % (waxy corn starch, WCS) to 0-25.91 % (SNPs), and the absorbance ratios of R1047/1022 decreased from 0.81 (WCS) to 0.60-0.76 (SNPs). The SNPs had lower thermal stability than that of WCS, characterized by a decrease in Td (temperature at maximum weight loss) from 309.39 °C (WCS) to 300.39-305.75 °C (SNPs). Furthermore, the SNPs exhibited excellent swelling power (3.48-28.02 %) and solubility (0.34-0.97 g/g). Notably, oil absorption capacity of the SNPs (9.77-15.67 g/g) was rather greater than that of WCS (1.33 g/g). Furthermore, the SNPs possessed the lower storage modulus (G'), loss modulus (G″) and viscosity than that of WCS. The SNPs with predictable size and high dispersion capability prepared in this study lay a foundation for expanding the application of SNPs.

α-Glucosidase inhibitory flavonol glycosides from Cyclocarya paliurus (Batalin) Iljinskaja and their kinetics characteristics.

Seven previously undescribed flavonol glycosides including four rare flavonol glycoside cyclodimers, dicyclopaliosides A-C (1-3) with truxinate type and dicyclopalioside D (4) with truxillate type, as well as three kaempferol glycoside derivatives cyclopaliosides A-C (5-7), were obtained from the leaves of Cyclocarya paliurus. Their structures were elucidated by extensive spectroscopic methods and chemical analyses. All compounds were evaluated for their inhibitory α-glucosidase activities. Among them, compounds 1-4 display strong inhibitory activities with IC50 values of 82.76 ± 1.41, 62.70 ± 4.00, 443.35 ± 16.48, and 6.31 ± 0.88 nM, respectively, while compounds 5-7 showed moderate activities with IC50 values of 4.91 ± 0.75, 3.64 ± 0.68, and 5.32 ± 0.53 µΜ, respectively. The structure-activity relationship analysis assumed that the cyclobutane cores likely contribute to the enhancement of α-glucosidase inhibitory activities of dimers. Also, the interaction mechanism between flavonol glycoside dimers and α-glucosidase were explored by the enzyme kinetic assay, indicating that compounds 1-3 exhibited mixed-type inhibition, while 4 showed uncompetitive inhibition. Additionally, the active compounds have also undergone molecular docking evaluation.

Liquid nitrogen ball-milled mechanochemical modification of starches with typically selected A, B and C crystal types on multiscale structure and physicochemical properties.

This study investigated the effect of liquid nitrogen ball-milled mechanochemical treatment on multiscale structure and physicochemical properties of starches with typically selected A (rice starch, ReS), B (potato starch, PtS) and C (pea starch, PeS) crystal types. The morphology of starch samples changed from integral granules to irregular fragments, and the interaction between the exposure OH bonds led to a serious agglomeration. As the treatment times extended, the crystalline structure of starch samples was gradually destroyed, and the excessive treatment approached amorphization. Moreover, the thermal stability of starch samples showed the downward tendency; and with amorphization increased, the swelling power (SP), solubility (S), water absorption capacity (WAC), oil absorption capacity (OAC) and hydrolysis rate of starch samples gradually increased. The obtained results provided a theoretical foundation for broadening the application range of ball-milled starches with different crystal types.

Golden Flower Tibetan Tea Polysaccharides Alleviate Constipation in Mice by Regulating Aquaporins-Mediated Water Transport System and Gut Microbiota.

Constipation, a widespread gastrointestinal disorder, often leads to the exploration of natural remedies. This study examines the efficacy of Golden Flower Tibetan Tea Polysaccharides (GFTTPs) in alleviating constipation in mice. Chemical analyses reveal that GFTTPs possess O-H, carboxyl, carboxylic acid (-COOH), and C-O-C groups, alongside a porous crystal structure with thermal stability. In animal experiments, GFTTPs significantly upregulated aquaporin 3 (AQP3) and aquaporin 8 (AQP8) expressions in the colon, enhancing water absorption and reducing fecal water content. At a 400 mg/kg dosage, GFTTPs notably improved colonic tissue alterations and serum levels of excitatory neurotransmitters caused by loperamide hydrochloride. They also beneficially altered gut microbiota, increasing Coprococcus, Lactobacillus, and Pediococcus populations. These changes correlated with improved stool frequency, consistency, and weight in constipated mice. Importantly, GFTTPs at 200 and 400 mg/kg doses exhibited comparable effects to the normal control group in key parameters, such as gastrointestinal transit rate and fecal moisture. These findings suggest that GFTTPs may serve as a potent natural remedy for constipation, offering significant therapeutic potential within the context of gut health and with promising implications for human applications.

Effective extraction of Xuetongsu and its role in preventing RA synovial hyperplasia by targeting synovial cell migration and apoptosis.

Kadsura heteroclita (Roxb) Craib also named Xuetong in Tujia ethnomedicine in China, has been traditionally employed in rheumatoid arthritis (RA) treatment. Our preceding investigations have elucidated that Xuetongsu (XTS), a triterpenoid compound predominant in Xuetong, showed excellent anti-RA-fibroblast-like synoviocytes (RAFLS) proliferation effect. However, XTS belongs to the trace components of the Xuetong plant, which poses certain limitations to the research. In this study, we designed a method that enhanced the extraction yield of XTS and explored the mechanism of its inhibition of RAFLS cell proliferation and migration in the treatment of RA. The results displayed that XTS reduced RAFLS cell proliferation, with an IC50 value of 4.68 ± 0.65 µM. A series of experimental techniques were utilized to show that XTS induce apoptosis in RAFLS cells at concentrations ranging from 4.5 to 18 µM, including wound healing assay, flow cytometry, and western blot analysis. Moreover, XTS at dosages of 0.42-0.84 mg/kg markedly attenuated paw swelling and synovial hyperplasia in arthritic rats, primarily through the inhibition of RAFLS migration and promotion of RAFLS apoptosis via High mobility group box 1 (HMGB-1)/Matrix metalloproteinase-9 (MMP-9)/MMP-13 signaling pathway and Bcl-2/Bax/Caspase-3 signaling pathway, respectively.

Mechanism of synergistic stabilization of emulsions by amorphous taro starch and protein and emulsion stability.

Amorphous taro starch (TS)/whey protein isolate (WPI) mixtures were prepared using pasting treatment. The TS/WPI mixtures and their stabilized emulsions were characterized to determine the emulsion stability and the mechanism of synergistic stabilization of emulsions. As WPI content increased from 0% to 13%, the paste final viscosity and retrogradation ratio of the TS/WPI mixture gradually decreased from 3683 cP to 2532 cP and from 80.65% to 30.51%, respectively. As the WPI content increased from 0% to 10%, the emulsion droplet size decreased gradually from 96.81 µm to 10.32 µm, and the storage modulus G' and stabilities of freeze-thaw, centrifugal, and storage increased gradually. Confocal laser scanning microscopy revealed that WPI and TS were mainly distributed at the oil-water interface and droplet interstice, respectively. Thermal treatment, pH, and ionic strength had little influence on the appearance but had different influences on the droplet size and G', and the rates of droplet size and G' increase under storage varied with different environmental factors.

MYPT1 inhibits the metastasis of renal clear cell carcinoma via the MAPK8/N-cadherin pathway.

Myosin phosphatase target subunit 1 (MYPT1) is a subunit of myosin phosphatase that is capable of regulating smooth muscle contraction. MYPT1 has been reported to be involved in a wide variety of tumours, but its expression and biological functions in renal clear cell carcinoma (ccRCC) remain obscure. Herein, we analysed the relationship between patient clinicopathological characteristics and MYPT1 expression levels in ccRCC patients using a tissue microarray (TMA) and data retrieved from the TCGA-KIRC dataset. MYPT1 was overexpressed or depleted using siRNA in ccRCC cells to assess the effects on migration and invasion in vitro and in vivo. Additionally, RNA-sequencing and bioinformatics analysis were performed to investigate the precise mechanism. MYPT1 expression in ccRCC tissues was observed to be lower than that in nonmalignant tissues (P < 0.05). In addition, MYPT1 downregulation was closely linked to advanced pathological stage (P < 0.05), and poor OS (overall survival; P < 0.05). Functionally, increased expression of MYPT1 suppressed ccRCC migration and invasion in vitro, and inhibited tumour metastasis in vivo. In addition, MYPT1 overexpression exerted its suppressive effects via the MAPK8/N-cadherin pathway in ccRCC.

Anti-RAFLS Triterpenoids and Hepatoprotective Lignans From the Leaves of Tujia Ethnomedicine Kadsura heteroclita (Xuetong).

A pair of 3,4-seco-cycloartane triterpenoid isomers with a rare peroxy bridge, namely, xuetonins A and B (1 and 2), four new lignans xuetonlignans A-D (3-6), a new sesquiterpene xuetonpene (7), and a new natural product xuetonin C (8), along with 43 known compounds, were obtained from the leaves of Tujia ethnomedicine, Kadsura heteroclita. Their structures and configurations were determined with the help of a combination of 1D- and 2D-NMR, HRESIMS spectra, electronic circular dichroism (ECD), and X-ray diffraction data. Compounds 2, 10, 13-15, and 17-19 showed moderate-to-potent activity against rheumatoid arthritis fibroblast-like synoviocytes (RAFLS) with IC50 values of 19.81 ± 0.26, 12.73 ± 0.29, 5.70 ± 0.24, 9.25 ± 0.79, 5.66 ± 0.52, 11.91 ± 0.44, 13.22 ± 0.27, and 15.94 ± 0.36 µM, respectively. Furthermore, compounds 22, 25, and 31 exhibited significant hepatoprotective effects against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells at 10 µM, and the cell viability increased by 12.93, 25.23, and 13.91%, respectively, compared with that in the model group (cf. bicyclol, 12.60%).

Anti-inflammatory and antioxidant activities of chemical constituents from the flower buds of Buddleja officinalis.

Five new glycosides including mimenghuasu A and B (1-2), isolinarin (3), cyclocitralosides A and B (4-5), along with forty-seven known compounds were isolated from the flower buds of Buddleja officinalis. These structures were elucidated by extensive spectroscopic analysis (UV, IR, 1 D, 2 D NMR, and MS spectra). The anti-inflammatory activities of the isolated compounds were determined by enzyme-linked immunosorbent assay (ELISA) on the expression of TNF-α (LPS-activated RAW264.7 cells) and MTT experiment on LPS-induced HUVECs proliferation effects. Good suppressive effects on the expression of TNF-α were shown by 4 and 5 with IC50 values of 19.35 and 22.10 µM, respectively, compared to positive control indomethacin (IC50 16.40 µM). In addition to this, some isolated compounds exhibited excellent antioxidant activities including compounds 16, 18, 29, 39, and 47 (IC50 µM: 82.59, 72.94, 33.65, 46.67, and 20.81, respectively) with almost the same or stronger potency with reference to vitamin C as positive control (IC50 81.83 µM).

Acupuncture combined with metformin versus metformin alone to improve pregnancy rate in polycystic ovary syndrome: A systematic review and meta-analysis.

Objective: The aim of this study was to evaluate the comparison between acupuncture combined with metformin versus metformin alone in improving the pregnancy rate of people with polycystic ovary syndrome (PCOS). Methods: A literature search of eight databases resulted in nine randomized controlled trials (RCTs) that assessed the effect of acupuncture combined with metformin on pregnancy rate in PCOS patients compared with metformin alone. Subsequently, data extraction and analysis were conducted to evaluate the quality and risk of bias of the methodological design of the study, and meta-analysis was conducted on the RCT data. Results: Nine RCTs and 1,159 women were included. Acupuncture can improve pregnancy rate. It was analyzed according to the diagnostic criteria of PCOS [Z = 2.72, p = 0.007, relative risk (RR) 1.31, 95% CI 1.08 to 1.60, p = 0.15, I 2 = 41%]. Analysis was performed according to different diagnostic criteria of pregnancy (Z = 3.22, p = 0.001, RR 1.35, 95% CI 1.13 to 1.63, p = 0.12, I 2 = 42%). Acupuncture can improve ovulation rate. Subgroup analysis was performed according to the number of ovulation patients (Z = 2.67, p = 0.008, RR 1.31, 95% CI 1.07 to 1.59, p = 0.04, I 2 = 63%) and ovulation cycle (Z = 3.57; p = 0.0004, RR 1.18, 95% CI 1.08 to 1.29, p = 0.57, I 2 = 0%). Statistical analysis also showed that acupuncture combined with metformin could improve homeostatic model assessment of insulin resistance (HOMA-IR) [mean difference (MD) -0.68, 95% CI -1.01 to -0.35, p = 0.003, I 2 = 83%]. Conclusions: Based on the results of this study, compared with metformin alone, acupuncture combined with metformin has a positive effect on pregnancy rate, ovulation rate, and insulin resistance in PCOS. However, due to the limitations regarding the number and quality of the included studies, the above conclusions need to be verified by further high-quality studies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero.

Sesquiterpenes from Kadsura coccinea attenuate rheumatoid arthritis-related inflammation by inhibiting the NF-κB and JAK2/STAT3 signal pathways.

The roots of Kadsura coccinea is commonly used in Tujia ethnomedicine, named "heilaohu", having the effect of treating rheumatic arthritis (RA). Chemical investigation on the ethanol extract of heilaohu led to the isolation of one undescribed cuparane sesquiterpenoid, heilaohusesquiterpenoid A, one undescribed carotane sesquiterpenoids, heilaohusesquiterpenoid B, and eighteen sesquiterpene derivatives. Their structures were subsequently determined based on their 1D and 2D-NMR, HR-ESI-MS, and ECD spectroscopic data. Gaultheriadiolide was the most cytotoxic compound against the proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells with an IC50 value of 9.37 µM. In the same line, nine compounds exhibited significant inhibition effects against TNF-α and IL-6 release in the LPS-induced RAW264.7 cells with IC50 values ranging between 1.03 and 10.99 µM. The potential molecular mechanisms of the active compounds against RA were established through pharmacological network analysis based on the initial screening results. Experimental validation showed that gaultheriadiolide suppressed inflammation by inhibiting the NF-kB and JAK2/STAT3 pathways. This study enriches the structural diversity of sesquiterpenes in K. coccinea and lays a foundation for further anti-RA and anti-inflammatory studies.