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Ethnopharmacological Relevance: Tongguanteng injection (TGT), the water extract from the stem of the Traditional Chinese hebal medicine of Marsdenia tenacissima (Roxb.) Wight et Arn. has been used as anticancer remedy for decades. TGT was not only used in the treatment of many malignant cancers extensively, but also an adjuvant anticancer drug with chemotherapeutics clinically., Aim of the Study: To evaluate the effects of TGT on reversing paclitaxel (PTX) resistance and investigate the potential mechanism related to TAB1 in ovarian cancer (OC) in vitro and in vivo., Materials and Methods: The synergistic effect and reversal ratio were determined by CCK8 assay and median-effect principle after the combination of TGT and PTX in OC A2780 and its PTX-resistant (A2780/T) cells. The biological functions in cell apoptosis, migration and invasion of A2780/T cells treated by PTX 4 μM with TGT 20, 40, 80 mg⋅mL -1 for 24 h were evaluated by colony formation, flow cytometry, wound healing and transwell assays. Proteomics technique and bioinformatic analysis were used to indentify the change of TAB1 expression in A2780/T cells induced by TGT. The association between TAB1 expression and human OC was analyzed by gene expression databases. In A2780/T cells, western blotting and colony formation assays were used to investigate the relationship between TAB1 expression and PTX resistance after TAB1 overexpression by TAB1 plasmids. The mechanism of TGT and PTX regulating TAB1 and its related proteins were explored by western blotting and flow cytometry assays after TAB1 knock-down using siTAB1. Moreover, TUNEL staining, immunohistochemistry (IHC) and histopathology were used to observe the antitumor effects, TAB1 and p-p38 expression and the tissues impairments in nude mice xenograft model established by A2780/T cells after the co-treatment with TGT and PTX by in vivo., Results: TGT combined with PTX showed the synergistic effect (CI<1), which could reverse the IC 50 values of PTX in OC A2780 and A2780/T cells about 23.50 and 6.44 times, respectively. Besides, TGT combined with PTX could significantly inhibit the migration, invasion and promote apoptosis of A2780/T cells. We identified that TGT could induce TAB1 expression in A2780/T cells by proteomics analysis. TAB1 downregulation was significantly associated with tumorigenesis and poor prognosis in OC patients and PTX resistance in A2780/T cells. Furthermore, TGT could activate TAB1/TAK1/p38 MAPK signaling pathway targeting TAB1 and regulate the expression of Bax, Bcl-2 proteins to improve the sensitivity of A2780/T cells to PTX. TGT combined with PTX also showed a greater inhibition in tumor growth than PTX monotherapy in vivo. These promising results show the efficacy of TGT in reversing PTX resistance and provide a potential strategy that targeting TAB1/TAK1/p38 MAPK signaling pathway may improve the chemotherapy sensitivity in OC., Conclusions: Our results revealed that Tongguanteng injection could reverse paclitaxel resistance and the potential mechanism might be associated with the activation of TAB1/TAK1/p38 MAPK signaling pathway in OC in vitro and in vivo. TAB1 might be a pivotal target for reversing PTX resistance. This study will provide a theoretical basis for the combination of Tongguanteng injection and paclitaxel in clinic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Two new dammarane-type triterpenoids, dammar-3 α ,12( R ),20( S )-triol-12,32( R );20,32-diepoxy-25-methy-25-en-tridecacyclic ether ( 1 ) and (23 E )-12 β ,20( R ),25( S ),26-tetrahydroxydammar-23-en-3-one ( 2 ) were isolated from the green walnut husks of Juglans mandshurica Maxim together with six known compounds. Their structures were elucidated through extensive spectroscopic analyses and by comparison with the literature, and the cytotoxic activities of these compounds were evaluated.

Four new flavonoids (1-4) and fourteen known compounds (5-18), were isolated from the aerial part of Bupleurum chinense DC. The structural determination of the new flavonoids was accomplished using comprehensive spectroscopic methods, including 1D and 2D NMR spectra with references to the literatures, as well as high-resolution mass spectrometric analysis. The anti-proliferative activities of the flavonoids (1-18) against HeLa cells were evaluated using the MTT assay with cisplatin as the positive control., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Four new indole alkaloids, daturametelindoles A-D (1-4) were isolated from the EtOAc soluble partition of the ethanol extract of the Datura metel seeds. The structures of the new compounds were determined based on spectroscopic evidence, including their 1D- and 2D-NMR spectra and mass spectrometry. In particular, compounds 1-4 were all racemes, confirmed by the optical rotations and CD spectra. Unfortunately, the chiral monomers were not obtained due to the amount, but the developments of their chiral separation and chiral resolution were completed. All isolated compounds were evaluated for cytotoxic effects against human gastric adenocarcinoma cells (SGC-7901), human hepatoma (Hepg2), and human breast cancer (MCF-7)., Competing Interests: Declaration of Competing Interest The authors of this manuscript have declared that no competing interests exist., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Five new α -tetralone glycosides, juglanbiosides A-E ( 1-5 ), together with an α -tetralone derivative ( 15 ) and nine known 1,4-naphthoquinones ( 6-14 ) were isolated from the 95% EtOH extract of green walnut husks of Juglans mandshurica Maxim. Their structures were elucidated by comprehensive spectroscopic methods ( 1 H, 13 C NMR, DEPT, HSQC, HMBC, CD, HR-ESI-MS). In vitro cytotoxicities of all the isolated compounds were evaluated against BGC-823, HCT-15 and K562 cancer cell lines.[Formula: see text].

Phytochemical investigation of the roots of Solanum melongena L. resulted in the isolation of ten terpenes and sixteen lignans, including a new triterpene saponin, officinoterpenoside E ( 1 ) and twenty-five known compounds ( 2-26 ). All compounds were firstly isolated from S. melongena except 2 , 13 , 21 , 22 . The structures of these compounds were determined by 1 D and 2 D NMR spectra referring to the literatures, together with high-resolution mass spectrometric analysis. All compounds were evaluated for the cytotoxicity against three cancer cell lines (HepG2, Hela, and MCF-7) in vitro . The results showed that compounds 1 , 6 , 20 , 25 and 26 exhibited moderate cytotoxicity against HepG2, Hela and MCF-7 cells with IC 50 values in the range of 16.8 ± 1.7 to 29.1 ± 1.9 μM. Therefore, these terpenoids and lignans may have potential biological activity, and also seemed to be of great chemotaxonomic value for S. melongena .

Background: The aim of the present study was to examine the effects of the Bolbostemma paniculatum (Maxim.) Franquet (BP) active compound, BP total saponins (BPTS), on MDA-MB-231 cells, and investigate the underlying mechanism regarding BPTS-mediated attenuation of the PI3K/Akt/mTOR pathway., Methods: The effect of BPTS on cytotoxicity, induction of apoptosis and migration on MDA-MB-231 cells at three different concentrations was investigated. A CCK-8 assay, wound-healing assay and flow cytometry were used to demonstrate the effects of BPTS. Additionally, expression of the primary members of the PI3K/Akt/mTOR signaling pathway was assessed using western blotting. To verify the underlying mechanisms, a PI3K inhibitor and an mTOR inhibitor were used., Results: BPTS inhibited proliferation of MDA-MB-231 cells with an IC 50 value of 10 μg/mL at 48 h. BPTS inhibited migration of MDA-MB-231 cells, and the western blot results demonstrated that BPTS reduced p-PI3K, p-Akt and p-mTOR protein expression levels in MDA-MB-231 cells. Additionally, the results were confirmed using a PI3K inhibitor and an mTOR inhibitor. BPTS decreased proliferation and migration of MDA-MB-231 cells possibly through inhibiting the PI3K/Akt/mTOR signaling pathway., Conclusions: The results highlight the therapeutic potential of BPTS for treating patients with triple-negative breast cancer.

A new triterpene named klodorol B (1), together with six known compounds, were isolated from the green walnut husks of Juglans mandshurica Maxim. Their structures were determined using spectroscopic methods on the basis of 1D and 2D NMR, and high-resolution electrospray ionization mass spectrometry. The isolated compounds were evaluated for their cytotoxic activities on human gastric carcinoma (BGC-823), human liver cancer (HepG-2) and human lung cancer (A549) cell lines. .

Two new glycosides including an alcohol glycoside and a phenolic glycoside: hexyl-1-O-α-d-arabinofuranosyl-(1 → 6)-β-d-glucopyranoside (1), 4-hydroxypropiophenone-4-O-β-d-glucopyranosyl(1 → 6)-β-d-glucopyranoside(2), along with six known naphthalenyl glucosides (3-8) were isolated from green walnut husks of Juglans mandshurica, and their structures were elucidated on the basis of spectroscopic studies. All compounds were evaluated for their inhibitory effects on tumour cells (BGC-823, HepG-2, MCF-7). The results showed that new compounds 1 and 2 had superior inhibitory activity in comparison with other naphthalenyl glucosides.

Objective: To study the anti-tumor chemical components of the pericarps of Juglans mandshurica., Methods: The chemical constituents were isolated and purified by AB-8 macroporous adsorption resin, silica gel, Sephadex LH-20 columns and recrystallization. The structures were elucidated on the basis of physicochemical properties and NMR spectral data analysis., Results: From the pericarps of Juglans mandshurica, twelve compounds were separated and identified as 3-methoxy juglone(1), 3-ethoxy juglone(2), 1,8-di-hydroxy anthraquinone (3), juglone (4), 2α, 3α, 19α-trihydroxy ursolic acid (5), 1α, 3β-dihydroxy-olean-18-ene (6), methyl gallate (7), pterocarine(8), quercetin(9), kaempferol(10), daucosterol(11), and β-sitosterol(12)., Conclusion: Compounds 1 - 3 and 6 are isolated from the pericarps of Juglans mandshurica for the first time. Compounds 5 and 7 are isolated from Juglans genus for the first time.

Stearic acid (SA) and poly (lactic-co-glycolic acid) (PLGA) grafted chitosan oligosaccharide (SA-CSO-PLGA SCP) tripolymer was synthesized via the reaction between the carboxyl group of SA or PLGA with carboxylic side group, and the amine group of CSO in the presence of 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The degrees of amino-substitution for SA and PLGA were assayed through 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) test and (13)C NMR spectrum, which were 8.15% and 5.82%, respectively; the critical micelle concentrations of SCP in PBS (pH 7.4) and deionized water (DI water) were about 34.9 and 14.5 microg/ml, respectively. Using 10-hydroxycamptothecin (HCPT) as a model drug, the drug-loaded micelles showed above 86% encapsulation efficiency, which not only enhanced the solubility of HCPT in aqueous medium markedly, but also protected the lactone ring of HCPT. Cellular uptakes of SCP micelles against A549, MCF-7 and HepG-2 tumor cells showed a faster cellular internalization. Comparing to the commercial HCPT injection, HCPT-loaded micelles showed higher cytotoxicities against A549, MCF-7 and HepG-2 cells. The increased folds were 22, 18 and 15, respectively. These results suggested the SCP could be applied as a carrier for hydrophobic drugs., (2010 Elsevier B.V. All rights reserved.)