Steroidal Saponins from Water Eggplant (Fruits of Solanum torvum) Exhibit Anti-Epileptic Activity against Pentylenetetrazole-Induced Seizure Model in Zebrafish.

The fruits of Solanum torvum Swartz, a wild relative of eggplant, are consumed as a wild vegetable in tropical regions of Africa, Asia, and South America. In traditional Chinese medicine, it is believed to have anti-inflammatory and sedative effects. In the Philippines, water decoction is used to treat hyperactivity disorder. Twenty-two steroidal saponins were isolated and purified from the fruits grown in Yunnan, China, including six new compounds: torvosides U-Z (1-6). During drying and cooking, the saponins may undergo transformation, resulting in small amounts of sapogenins. These transformations can include dehydration of hydroxyl groups at position C22, formation of double bonds at position 20, 22 or 22, 23, and even formation of peroxide products. Saponin compounds torvoside X (4), torvoside Y (5), torvoside A (7), and (25S)-3-oxo-5α-spirostan-6α-yl-O-ß-d-xylopyranoside (20), which are glycosylated at C-6, showed certain anti-epileptic activity in a pentylenetetrazole-induced zebrafish seizure model. No antiproliferative activity was detected when tested on the cancer cell line HepG2, and no hepatotoxic effect was noted on normal liver cell line LO2.

Tsaokoflavanols A1-J1: Flavanol-fatty alcohol hybrids with HPL inhibitory activity from Amomum tsao-ko.

Ten previously undescribed compounds were isolated from the fruits of Amomum tsao-ko (Zingiberaceae), including nine undescribed flavanol-fatty alcohol hybrids (1-6, 10-11, 13), and a flavanol-monoterpenoid hybrid (14), along with seven known flavanol hybrids (7-9, 12, 15-17). The structures of these compounds were determined using various analyses, such as HRESIMS, 1D/2D NMR, and ECD calculations. In terms of biological activity, compounds 1, 2, 5, and 6 exhibited inhibitions of human pancreatic lipase (HPL), with IC50 values ranging from 0.017 to 0.193 mM. Some of these values were found to be stronger than that of the positive control, orlistat (IC50, 0.067 mM). Molecular docking studies were also conducted to investigate the interactions between these compounds and HPL. The docking simulations revealed the importance of the orientation of the 3,4-dihydroxyphenyl in binding with HPL. Additionally, compound 9 demonstrated cytotoxicity against HepG2, with a CC50 value of 14.96 ± 0.62 µM as determined by the MTT assay. Flow cytometry analysis indicated that compound 9 induced apoptosis in HepG2 cells. Western blot results showed an up-regulation of apoptosis-related proteins, such as p53 protein, Bax and Caspase-3 proteins, while the expression of Bcl-2 protein was down-regulated.

Sesquiterpenoids from aged Artemisia argyi and their 3D-QSAR for anti-HBV activity.

Artemisia argyi Levl. Et Vant, commonly known as "Chinese Mugwort," has been utilized in traditional Chinese medicine and cuisine for centuries. Aged Chinese Mugwort has been uncovered to possess superior quality and safety, and its ethyl acetate extract has been found to exhibit anti-hepatitis B virus (HBV) activity. In this study, twenty-five sesquiterpenoids were isolated and characterized from three-year-aged A. argyi. Among them, 14 previously undescribed sesquiterpenoids (1-14), featuring double bond oxidation or ring opening. It is hypothesized that during the aging process, sesquiterpenes undergo oxidative transformation of their double bonds to form alcohols due to external factors and inherent properties. The anti-HBV activity and cytotoxicity of all compounds were assessed in vitro using HepG 2.2.15 cells, and their structure-activity relationships were analyzed through three-dimensional quantitative structure-activity relationship (3D-QASR) techniques. The α-methylene-γ-lactone sesquiterpenoid derivatives were discovered to have potent inhibitory activity against HBV. This research may broaden the potential applications of Chinese Mugwort and offer further guidance for its development and utilization as functional food or traditional Chinese medicine.

Efficacy of first-line immunization combined with antiangiogenesis treatment and chemotherapy for the treatment of tongue cancer: A case report.

BACKGROUND: There is currently no uniform and effective treatment for patients with locally advanced oral cancer who cannot tolerate surgery or radiotherapy. The prognosis of oral cancer patients with lymph node metastasis is very poor, but the clinical treatment of such patients faces certain challenges. PATIENTS AND METHODS: Case 1 was a 59-year-old patient with tongue cancer (cT 3 N x M 0 G 2) who refused radiotherapy because of a history of leukoderma. After evaluation of disease condition, a 4-drug combination therapy of toripalimab + anlotinib + nabpaclitaxel + carboplatin was administered. Case 2 was a 55-year-old patient with tongue cancer (cT 3 N 2 M 0 G 1) who could not receive radiotherapy because of a medical history of cervicofacial burns. After disease evaluation, toripalimab + anlotinib + docetaxel + carboplatin combination therapy was administered. CASE SUMMARY: Both patients did not experience any adverse reactions during treatment and achieved a complete response after 2 cycles of treatment. Their progression-free survival is currently 6 and 8 months, respectively, and they are in sustained remission. CONCLUSION: Currently, the efficacy of immune checkpoint inhibitors targeting programmed death-1 as a first-line treatment of inoperable and non-radiatable locally advanced oral cancer is unknown. Here, we describe 2 cases of locally advanced oral cancer treated with first-line immune checkpoint inhibitors in combination with targeted therapy and chemotherapy. This approach was successful in these patients, but a larger sample size is required to verify our findings.

Preparation and characterization of PA/P(AA-co-AM) composite hydrogels via photopolymerization.

The present study synthesized a deep eutectic solvent (DES) using acrylic acid (AA), acrylamide (AM), and choline chloride (ChCl), and added phytic acid (PA) as a filler. Subsequently, the PA/P(AA-co-AM) composite hydrogel was prepared under ultraviolet irradiation and used a photoinitiator. Characterization of the hydrogels was conducted using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The study aimed to investigate the impact of PA on the mechanical properties, fatigue resistance, and electrical conductivity of the composite hydrogel. The findings demonstrated that as the mass fraction of PA increased, the compressive strength of the composite hydrogel gradually decreased, yet the fatigue resistance of the composite hydrogel increased. Specifically, after 10 cycles of compression, the resilience recovery rate of FP0 dropped from 86.9% to 70.4%, the maximum stress recovery rate of FP1 dropped from 97.9% to 89.4%, the maximum stress recovery rate of FP2 dropped from 94.4% to 86.6%, and the maximum stress recovery rate of FP3 dropped from 97.3% to 93%. Overall, this study offers a straightforward and efficient method for producing composite hydrogels with both fatigue resistance and electrical conductivity.

Undescribed amino acid-sesquiterpene lactone adducts and sesquiterpene glycosides from the roots of Saussurea lappa and their anti-HBV activity.

Saussurea lappa (Asteraceae family), a traditional Chinese medicine, has been found to possess anti-inflammatory, immune-promoting, antibacterial, antitumor, anti-HBV, cholestatic, and hepatoprotective activities. Herein, two undescribed amino acid-sesquiterpene lactone adducts, saussureamines G and H (1 and 2), and two new sesquiterpene glycosides, saussunosids F and G (3 and 4), along with 26 known sesquiterpenoids (5-30) have been isolated from the roots of S. lappa. Their structures and absolute configurations of these compounds were established by physical data analyses such as HRESIMS, IR, 1D and 2D NMR and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (5, 6, 12, 13, 17, 19, 23, 26, 29, and 30) exhibited activities against the secretions of HBsAg and HBeAg. In particular, compound 6 showed inhibition of HBsAg and HBeAg secretion with IC50 values of 11.24 and 15.12 µM, with SI values of 1.25 and 0.93, respectively. Molecular docking studies were also conducted on the anti-HBV compounds. Overall, this study provides insights into the potential therapeutic uses of the compounds found in the roots of S. lappa, particularly in the treatment of hepatitis B virus infections.

Artemiprinolides A-M, thirteen undescribed sesquiterpenoid dimers from Artemisia princeps and their antihepatoma activity.

Bioassay-guided investigation of the active fraction of Artemisia princeps led to 13 undescribed sesquiterpenoid dimers, artemiprinolides A-M (1-13), together with 11 known ones (14-24). Their structures were elucidated by comprehensive spectroscopic data and absolute configurations were assigned based on single crystal X-ray diffraction data and ECD calculations. Structurally, all compounds were postulated to be derived from the Diels-Alder cycloaddition. The isolated dimers except 11 and 15 were assayed for their cytotoxicity against HepG2, Huh7, and SK-Hep-1 cell lines, of which four compounds (3, 13, 17, 18) exhibited obvious cytotoxicity with IC50 values ranging from 8.8 to 20.1 µM. Interestingly, the most active compounds 1 and 16 manifested significant cytotoxicity on the three tested hepatoma cell lines with IC50 values of 5.4, 4.1 (HepG2), 7.7, 5.6 (Huh7), and 11.8, 15.7 µM (SK-Hep-1), respectively, which were better than sorafenib. Compound 1 dose-dependently inhibited cell migration and invasion, and significantly induced the HepG2 cell arrest in G2/M phase by downregulating cdc2 and pcdc2 and upregulating cyclinB1; and induced apoptosis by downregulating Bcl-2 expression and upregulating Bax level. The molecular docking study implied that the carbonyl at the C-12' of 1 had a strong binding affinity with PRKACA.

Study on Chemical Constituents of Panax notoginseng Leaves.

Panax notoginseng (Burk.) F. H. is a genuine medicinal material in Yunnan Province. As accessories, P. notoginseng leaves mainly contain protopanaxadiol saponins. The preliminary findings have indicated that P. notoginseng leaves contribute to its significant pharmacological effects and have been administrated to tranquilize and treat cancer and nerve injury. Saponins from P. notoginseng leaves were isolated and purified by different chromatographic methods, and the structures of 1-22 were elucidated mainly through comprehensive analyses of spectroscopic data. Moreover, the SH-SY5Y cells protection bioactivities of all isolated compounds were tested by establishing L-glutamate models for nerve cell injury. As a result, twenty-two saponins, including eight dammarane saponins, namely notoginsenosides SL1-SL8 (1-8), were identified as new compounds, together with fourteen known compounds, namely notoginsenoside NL-A3 (9), ginsenoside Rc (10), gypenoside IX (11), gypenoside XVII (12), notoginsenoside Fc (13), quinquenoside L3 (14), notoginsenoside NL-B1 (15), notoginsenoside NL-C2 (16), notoginsenoside NL-H2 (17), notoginsenoside NL-H1 (18), vina-ginsenoside R13 (19), ginsenoside II (20), majoroside F4 (21), and notoginsenoside LK4 (22). Among them, notoginsenoside SL1 (1), notoginsenoside SL3 (3), notoginsenoside NL-A3 (9), and ginsenoside Rc (10) showed slight protective effects against L-glutamate-induced nerve cell injury (30 µM).

Artemyrianosins A-J, cytotoxic germacrane-type sesquiterpene lactones from Artemisia myriantha.

Ten new germacrane-type sesquiterpenoids, artemyrianosins A-J (1-10), were isolated from the aerial parts of Artemisia myriantha. Their structures were elucidated by spectral analyses including UV, IR, HRESIMS, 1D and 2D NMR, ECD and the absolute configurations of compounds 1 and 7-9 were characterized using X-ray crystallography. All isolates were tested their cytotoxicity against three human hepatoma cell lines (HepG2, Huh7, and SK-Hep-1), and compounds 1-3, 7, and 10 showed cytotoxicity with IC50 values ranging from 43.7 to 89.3 µM. Among them, the most active compound 3 exhibited activity against three human hepatoma cell lines with IC50 values of 43.7 µM (HepG2), 47.9 µM (Huh7), and 44.9 µM (SK-Hep-1).

Structure-Based Molecular Networking for the Discovery of Anti-HBV Compounds from Saussurea lappa (Decne.) C.B Clarke.

It is a crucial to find target compounds in natural product research. This study presents a concept of structure-guided isolation to find candidate active molecules from herbs. We establish a process of anti-viral sesquiterpene networking. An analysis of the networking suggested that new anti-HBV sesquiterpene may be attributable to eudesmane-, guaiane-, cadinane-, germacane- and bisabolane-type sesquiterpenes. In order to evaluate the efficiency of the structure-based molecular networking, ethanol extract of Saussurea lappa (Decne.) C.B Clarke was investigated, which led to the isolation of two guaiane-type (1 and 14), ten eudesmane-type (2-5 and 8-13), two chain (6 and 7) and one germacrane-type (15) sesquiterpenes, including seven new ones, lappaterpenes A-G (1-7), which are reported on herein. The absolute configurations of the new compounds were established by coupling constants, calculated ECD and ROESY correlations, as well as comparisons of optical rotation values with those of known compounds. The absolute configuration of compound 2 was further confirmed by X-ray diffraction. Compounds 1-15 were evaluated for their potency against hepatitis B virus. Compounds 4, 6, 7 and 9 showed effect on HBsAg with inhibition ratios of more than 40% at 30 µM concentrations. Compounds 14 and 15 inhibited HBsAg secretion with the values of IC50 0.73 ± 0.18 and 1.43 ± 0.54 µM, respectively. Structure-based molecular networking inspired the discovery of target compounds.

Biomimetic Synthesis of Lavandiolides H, I, and K and Artematrolide F via Diels-Alder Reaction.

The biomimetic synthesis of guaianolide dimers lavandiolides H, I, and K and artematrolide F containing a spirolactone moiety has been accomplished for the first time from naturally abundant arglabin in four to six steps with an overall yield up to 60%, and a series of natural product-like guaianolide dimers, trimer, and tetramer were also successfully synthesized. Notably, the trimeric compound exhibited antihepatoma cytotoxicity more potent than that of sorafenib with IC50 values of 6.2 µM (HepG2), 6.8 µM (Huh7), and 7.2 µM (SK-HEP-1).

Artematrolide A inhibited cervical cancer cell proliferation via ROS/ERK/mTOR pathway and metabolic shift.

BACKGROUND: Artematrolide A (AR-A), a guaianolide dimer isolated from Artemisia atrovirens, demonstrated significant inhibitory effect on three human hepatoma cell lines (HepG2, Huh7 and SMMC7721). The anti-cervical cancer effect and mechanism of this compound have yet to be explored. This study is to reveal the role and mechanisms of artematrolide A on cervical cancer cells, and provide the pharmacological understanding of artematrolide A. PURPOSE: To investigate the function and possible mechanism of artematrolide A on cervical cancer cells in vitro. METHODS: HeLa S3 and SiHa cells were treated with artematrolide A at various concentrations. In this study, MTT, colony formation, cell migration and invasion, cell cycle analysis, cell apoptosis, reactive oxygen species (ROS) detection, western blotting, enzyme activity, and lactate production of artematrolide A were evaluated. RESULTS: Artematrolide A inhibited cell viability, proliferation, migration and invasion in a dose-dependent manner, caused cell cycle arrest in G2/M phase, and induced cell apoptosis via Bcl-2/PARP-1. The mechanism of action of artematrolide A included two aspects: artematrolide A suppressed cell proliferation by activating ROS/ERK/mTOR signaling pathway and promoted glucose metabolism from aerobic glycolysis to mitochondrial respiration by activating pyruvate dehydrogenase complex (PDC) and oxoglutarate dehydrogenase complex (OGDC) via inhibiting the activity of alkaline phosphatases (ALP). CONCLUSION: Artematrolide A exhibited a significant cytotoxic activity on cervical cancer cells, induced G2/M cell cycle arrest and apoptosis by activating ROS/ERK/mTOR signaling pathway and promoting metabolic shift from aerobic glycolysis to mitochondrial respiration, which suggested artematrolide A might be a potential agent for the treatment of cervical cancer.

New guaiane-type sesquiterpenoid dimers from Artemisia atrovirens and their antihepatoma activity.

Leading by cytotoxicity against HepG2 cells, bioactivity-guided fractionation of the EtOAc fraction from Artemisia atrovirens led to the isolation of 18 new guaianolide dimers, artematrolides A-R and lavandiolides A, B, C, H, and J. Eight compounds (1, 4, 10, 12, 13, and 19-21) were unambiguously confirmed by the single-crystal X-ray diffraction analyses, and the others were elucidated based on IR, UV, HRESIMS, 1D and 2D NMR experiments, and comparison of the experimental and calculated ECD data. Structurally, all of them were [4 + 2] Diels-Alder adducts of two monomeric guaianolides. The isolates were evaluated for their cytotoxicity against three human hepatoma cell lines, and 19 compounds demonstrated cytotoxicity against HepG2, SMMC-7721, and Huh7 cell lines. Especially, compounds 1, 12, 14, and 15 exhibited cytotoxicity with IC50 values of 4.4, 3.8, 7.6, and 6.7 µmol/L (HepG2), 9.6, 4.6, 6.6, and 6.0 µmol/L (SMMC-7721), and 7.6, 4.5, 6.9, and 5.6 µmol/L (Huh7), respectively. Notably, compound 12 showed the most promising activity against three human hepatoma cell lines and dose-dependently inhibited cell migration and invasion, induced G2/M cell cycle arrest and cell apoptosis in HepG2 cells, down-regulated the expression of BCL-2 and PARP-1, and activated PARP-1 to up-regulate the expression of cleaved-PARP-1.

Artematrovirenins A-P, guaiane-type sesquiterpenoids with cytotoxicities against two hepatoma cell lines from Artemisia atrovirens.

Random screening revealed that the EtOH extract of Artemisia atrovirens showed significant cytotoxicity against two human hepatoma cell lines (HepG2 and Huh7) with the inhibitory ratio of 98.9% and 99.7% at the concentration of 100 µg/mL. Further bioactivity-guided isolation of active fraction led to 16 new guaiane-type sesquiterpenoids, artematrovirenins A-P (1-16). Their structures were elucidated by extensive spectroscopic data. The absolute stereochemistry of compounds 1 and 14 was determined by single-crystal X-ray diffraction analyses. Pharmacological evaluation suggested that five compounds (3, 5, 8, 10, and 15) exhibited cytotoxicity, compounds 3 and 5 displayed cytotoxicity against HepG2 cell line with an IC50 values of 8.0 and 16.0 µM, as well as against Huh7 cell line with values of 18.2 and 32.2 µM.

Artatrovirenols A and B: Two Cagelike Sesquiterpenoids from Artemisia atrovirens.

Artatrovirenols A and B (1 and 2), two novel cagelike sesquiterpenoids, possess a unique 5/5/6/5/5-pentacyclic and a 5/5/6/5-tetracyclic system with an unprecedented tetracyclo[5.3.1.1.4,1101,5]dodecane scaffold from Artemisia atrovirens. The structures of compounds 1 and 2 including their absolute stereochemistry were elucidated through extensive spectroscopic analyses, X-ray crystallography, and quantum chemical calculations. Plausible biosynthetic pathways for the new isolates were proposed from the naturally occurring arglabin (3) via the key intramolecular Diels-Alder cycloaddition. Compound 1 showed cytotoxicity against three human hepatoma cell lines (HepG2, SMMC-7721, and Huh7) with half maximal inhibitory concentration values of 123.8, 44.0, and 142.6 µΜ, respectively.

Artemyrianolides A-S, Cytotoxic Sesquiterpenoids from Artemisia myriantha.

Random screening suggested that the EtOH extract of Artemisia myriantha (Asteraceae) and its EtOAc fraction had cytotoxicity against HepG2 cells with inhibitory ratios of 30.6% and 53.5% at 50.0 µg/mL. Bioassay-guided isolation of the most active fractions (Fr. C and Fr. D) afforded 19 new sesquiterpenolides, artemyrianolides A-S (1-19), involving 13 germacranolides (1-13), four guaianolides (14-17), and two eudesmanolides (18 and 19), together with 16 known sesquiterpenoids (20-35). The new compounds were characterized by physical data analyses (HRESIMS, IR, 1D and 2D NMR, ECD), and the absolute configurations of compounds 1, 2, and 11 were determined by X-ray crystallography. Structurally, compounds 2 and 11-13 maintain an uncommon cis-fused 10/5 bicyclic system and compound 12 possesses an unusual (7S) configuration. Twenty of the compounds exhibited cytotoxicity against HepG2, Huh7, and SMMC-7721 cell lines. Compound 9 showed cytotoxic activity on both HepG2 and Huh7 cells with IC50 values of 8.6 and 8.8 µM, and compounds 8 and 33 showed cytotoxicity to the three human hepatoma cell lines with IC50 values of 4.9 and 7.4 µM (HepG2), 4.3 and 7.8 µM (Huh7), and 3.1 and 9.8 µM (SMMC-7721), respectively.

Cytotoxic sesquiterpenoids against hepatic stellate cell line LX2 from Artemisia lavandulaefolia.

The preliminary assay suggested that the EtOH extract of Artemisia lavandulaefolia had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with an inhibitory ratio of 94.1% at 400 µg/mL. Bioassay-guided investigation led to eleven new sesquiterpenoids, artemilavanolides C-F (1-4) and artemlavandulolides A-G (5-11), as well as thirteen known compounds (12-24). Their structures were elucidated by extensive spectroscopic data and X-ray crystallographic analysis. Cytotoxicity evaluation suggested that fourteen compounds exhibited activity against HSC-LX2; compounds 22, 23 and 24 were comparable to the positive control, silybin (IC50, 162.3 µM); compounds 6, 9 and 16 showed moderate activity with IC50 values of 109.3, 114.0 and 124.2 µM. Importantly, compounds 14, 15 and 18 displayed significant cytotoxicity against HSC-LX2 with IC50 values of 52.1, 16.5 and 21.3 µM, and inhibitory activity on the deposition of human collagen type I (Col I) and human laminin (HL) with IC50 values ranging from 7.3 to 71.6 µM and from 18.6 to 72.9 µM.

Artemlavanins A and B from Artemisia lavandulaefolia and Their Cytotoxicity Against Hepatic Stellate Cell Line LX2.

Two new sesquiterpenoids, artemlavanins A (1) and B (3), together with fifteen known compounds (2 and 4-17) were isolated from the EtOH extract of Artemisia lavandulaefolia. The structures of new compounds were elucidated by extensive spectroscopic analyses (HRESIMS, 1D and 2D NMR) and ECD calculations. Compound 1 was a sesquiterpenoid lactone possessing a rearranged eudesmane skeleton; compounds 2-5, 6-8, 9 and 10-12 belonged to the eudesmane, guaiane, oppositane and farnesane sesquiterpenoids, respectively; compounds 13-17 were the phenyl derivatives with a 4-hydroxyacetophenone moiety. Twelve compounds (1-3, 5-7, 10-12, 14, 15 and 17) displayed cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values ranging from 35.1 to 370.3 µM. Compounds 2, 7, 10-12 and 17 exhibited the stronger cytotoxicity than silybin (IC50, 169.6 µM) with IC50 values of 82.1, 35.1, 95.0, 83.8, 81.6 and 90.1 µM. Compound 7 as the most active one showed significant inhibition on the deposition of human collagen type I (Col I), human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 10.7, 24.5 and 13.3 µM.

Artemyrianins A-G from Artemisia myriantha and Their Cytotoxicity Against HepG2 Cells.

Four new sesquiterpenoids, artemyrianins A-D (1-4), and three new norlignans, artemyrianins E-G (5-7), together with five known compounds (8-12), were isolated from the aerial parts of Artemisia myriantha (Asteraceae). The new compounds were established by spectroscopic data analyses (HRMS, IR, 1D and 2D NMR), and their absolute configurations were confirmed by the single-crystal X-ray diffraction or ECD calculations. The isolates showed cytotoxicity against HepG2 cells with IC50 values ranging from 33.3 to 145.2 µM.

Spiroseoflosterol, a Rearranged Ergostane-Steroid from the Fruiting Bodies of Butyriboletus roseoflavus.

Spiroseoflosterol (1), a 7(8→9)-abeo-ergostane steroid with a unique spiro[4.5]decan-6-one system, was isolated from the fruiting bodies of Butyriboletus roseoflavus. Its structure was determined by interpretation of comprehensive spectroscopic, X-ray, and computational data. A plausible biogenetic pathway for spiroseoflosterol (1) was postulated based on a key semipinacol rearrangement. Compound 1 was cytotoxic to HepG2 and Huh7/S (sorafenib-resistant Huh7) with IC50 values of 9.1 and 6.2 µM, respectively.