Jian-Yong Zhu

Labdane-type diterpenoids from the fruits of Vitex trifolia.

Seven new labdane-type diterpenoids, vitextrifolins A-G (1-7), along with eight previously reported analogues, were isolated from the fruits of Vitex trifolia. The structures of 1-7 were elucidated by spectroscopic data interpretation. The isolates were evaluated for their cytotoxicity against four human cancer cell lines (A549, HCT116, HL-60, and ZR-75-30), but all were inactive (IC(50) < 5 μg/mL).

Autophagy regulated by lncRNA HOTAIR contributes to the cisplatin-induced resistance in endometrial cancer cells

ObjectivesTo identify whether lncRNAs (long non-coding RNA) participate in the regulation of cisplatin-resistant induced autophagy in endometrial cancer cells.ResultsAutophagy activity was significantly boosted in cisplatin-resistant Ishikawa cells, a human endometrial cancer cell line, compared with that in parental Ishikawa cells. After analyzing the overall long noncoding RNA (lncRNA) profiling, a meaningful lncRNA, HOTAIR, was identified. It was down-regulated simultaneously in cisplatin-resistant Ishikawa cells and parental Ishikawa cells treated with cisplatin. RNA interference of HOTAIR reduced the proliferation of cisplatin-resistant Ishikawa cells and enhanced the autophagy activity of cisplatin-resistant Ishikawa cells with or without cisplatin treatment, in addition, beclin-1, multidrug resistance (MDR), and P-glycoprotein (P-gp) were mediated by lncRNA HOTAIR.ConclusionsIt is clear that lncRNAs, specifically HOTAIR, can regulate the cisplatin-resistance ability of human endometrial cancer cells through the regulation of autophagy by influencing Beclin-1, MDR, and P-gp expression.

Diterpenoids with thioredoxin reductase inhibitory activities from Jatropha multifida.

Abstract Chemical investigation of the Jatropha multifida has led to the isolation of nine diterpenoids (1–9), including a new jatromulone A, four podocarpane diterpenoids (2–5), two lathyrane-type diterpenoids (6 and 7) and two dinorditerpenoids (8 and 9). Their structures were elucidated by spectroscopic analysis, and the absolute configurations of 1 were determined by CD analysis. All of the diterpenoids were screened for inhibitory activity against thioredoxin reductase (TrxR), which is a potential target for cancer chemotherapy with redox balance and antioxidant functions. Compounds 6 and 7 exhibited stronger activity (IC50: 23.4 and 10.6 μM, respectively) than the positive control, curcumin (IC50 = 25.0 μM). Compounds 2–9 were isolated from J. multifida for the first time.

Anti-inflammatory effect of Man-Pen-Fang, a Chinese herbal compound, on chronic pelvic inflammation in rats

ETHNOPHARMACOLOGICAL RELEVANCE Traditional Chinese Medicine (TCM) has become the focus of research for the treatment of chronic pelvic inflammatory disease (CPID) based on unique medical theory system. Man-Pen-Fang (MPF), a Chinese herbal compound, which is composed of Thlaspi arvense L. (Cruciferae), Gleditsia sinensis Lam. (Leguminosae), Smilax china L. (Liliaceae), Euonymus alatus (Thunb.) Sieb. (Celastraceae) and Vaccaria segetalis (Neck.) (Caryophyllaceae) MPF has been used for the treatment of CPID and exerted significant clinical curative effects. However, the corresponding active principles and anti-inflammatory mechanism of MPF are still unknown. AIM OF THE STUDY The objective of present study is to evaluate the effect of MPF on CPID in the chronic pelvic inflammation (CPI) rat model and elucidate its possible anti-inflammatory mechanism. MATERIALS AND METHODS The CPI in rats was induced by administration with E. coli, Staphylococcus aureus and Beta-hemolytic streptococcus. MPF (8.112g/(kg d) (20 times of adult dosage), 4.056g/(kg d) (10 times of adult dosage) and 2.028g/(kg d) (5 times of adult dosage)) and Jingangteng Capsule 2g/(kg d) (20 times of adult dosage) were administered orally for 20 days. The serum levels of five inflammation-associated cytokines (IL-2, IL-6, IL-10, TNF-α and TGF-β1) were determined by enzyme-linked immunoassay, and the mRNA expression levels of TGF-β1, P53, Fas, FasL and MMP-2 in the uterus tissue were measured by quantitative RT-PCR. Furthermore, the expression of NF-κB p65 in uterus and ovary tissues was detected by immunohistochemistry assay and the pathological changes induced in the uterus and ovary tissues were observed by histology. RESULTS MPF caused a reduction in serum levels of IL-2, IL-6, IL-10, TNF-α and TGF-β1. The expression of P53 mRNA, Fas/FasL mRNA and MMP-2 mRNA in the uterus tissue was significantly elevated after treating with MPF, in contrast the expression of TGF-β1 mRNA was decreased. Furthermore, the expression of NF-κB p65 in uterus and ovary tissue was inhibited after treating with MPF. CONCLUSIONS These results taken together suggest that MPF has a significant anti-CPID effect, probably due to inhibition of the inflammation reaction by the promotion, and the induction of the apoptosis of inflammatory cells and downregulation of the serum levels of inflammation cytokines.

Antitumor Activity of Diterpenoids from Jatropha gossypiifolia: Cell Cycle Arrest and Apoptosis-Inducing Activity in RKO Colon Cancer Cells

Nine new minor diterpenoids, jatrogossones A-I (1-9), and six known analogues (10-15) were separated from an extract of the branches and leaves of Jatropha gosspiifolia. Compounds 4-6 and 10, possessing a 5/11 fused-ring skeleton, and 8, 9, and 13, with a 5/9/5 fused-ring skeleton, represent rare diterpenoid skeletons that have been found only in compounds isolated from plants of the Jatropha genus. The absolute configurations of 1-10 were defined by using a combination of electronic circular dichroism data analysis and single-crystal X-ray diffraction data. The cytotoxicity of the diterpenoids was evaluated using RKO and LOVO colon cancer cells in which regenerating islet-derived protein 3-alpha (Reg3A) is highly expressed. Compound 12 exhibited cytotoxicity against RKO colon cancer cells with an IC50 value of 2.6 μM. Morphological features of apoptosis and antimigration activities were evaluated in 12-treated RKO cells. Compound 12 effectively induced apoptosis of RKO, which was associated with G2/M-phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 12 significantly induced RKO cell apoptosis in a dose-dependent manner.

Saikosaponins: a review of pharmacological effects

Abstract Over the past decades, a number of phytochemicals have been reported to possess potent pharmacological effects. Saikosaponins represent a group of oleanane derivatives, usually as glucosides, which are commonly found in medicinal plants Bupleurum spp., which have been used as traditional Chinese medicine for more than 1,000 years in China. Emerging evidence suggests that saikosaponins have many pharmacological effects, including sedation, anticonvulsant, antipyretic, antiviral, immunity, anti-inflammation, antitumor properties, protecting liver and kidney and so on. The present review provides a comprehensive summary and analysis of the pharmacological properties of saikosaponins, supporting the potential uses of saikosaponins as a medicinal agent.

New tetracyclic triterpenoids from Jatropha gossypiifolia induce cell-cycle arrest and apoptosis in RKO cells

Four new tetracyclic-type triterpenoids, jatrogossols A - D (1-4), along with 5 known analogues (5-9), were isolated from the ethanol extract of the branches and leaves of Jatropha gossypiifolia. The absolute configurations of 1-4 were defined by using a combination of electronic circular dichroism data analysis and single-crystal X-ray diffraction data. The cytotoxicities of the triterpenoids were evaluated using RKO and HepG2 human cancer cell lines. Compound 8 was cytotoxic against RKO colon cancer cells with an IC50 value of 12.5 μM. The morphological features of apoptosis were evaluated in 8-treated RKO cells. Compound 8 effectively induced apoptosis of RKO, which was associated with G1 or S phase cell cycle arrest. Flow cytometric analysis showed that treatment with 8 significantly induced RKO cell apoptosis in a dose-dependent manner.

ARHGAP9 suppresses the migration and invasion of hepatocellular carcinoma cells through up-regulating FOXJ2/E-cadherin

Rho GTPase activating protein 9 (ARHGAP9), a member of RhoGAP family, has been identified as a RhoGAP for Cdc42 and Rac1. Here, we aimed to clarify the expression and functional role of ARHGAP9 in hepatocellular carcinoma (HCC). By analyzing TCGA (The Cancer Genome Atlas) LIHC (liver hepatocellular carcinoma) database, we found that ARHGAP9 expression was lower in HCC tissues than in normal liver tissues, and that patients with ARHGAP9 lower expression had a significant shorter overall survival time than those with ARHGAP9 higher expression. Cell counting kit-8 (CCK-8), transwell assays and in vivo experimental lung metastasis assay revealed that ARHGAP9 overexpression could inhibit HCC cell proliferation, migration and invasion, as well as HCC lung metastases. By next-generation RNA-sequencing, we identified that a transcription factor, Forkhead Box J2 (FOXJ2), was significantly induced by ARHGAP9 overexpression in HepG2 cells. Ectopic expression of FOXJ2 in HCC cell lines also exerted inhibitory effects on cell migration and invasion. Moreover, the inhibitory effects of ARHGAP9 on HCC cell migration and invasion was significantly attenuated by FOXJ2 knockdown. Luciferase reporter assay demonstrated that ARHGAP9 enhanced the transcription of E-cadherin (CDH1) via FOXJ2. Chromatin immunoprecipitation (ChIP) assay demonstrated that FOXJ2 modulated the transcription of E-cadherin (CDH1) by directly binding to its promoter. Furthermore, Pearson’s correlation analysis indicated that the mRNA levels of ARHGAP9 in HCC tissues were positively correlated with the mRNA levels of FOXJ2 and CDH1. These data clearly show that ARHGAP9/FOXJ2 inhibit cell migration and invasion during HCC development via inducing the transcription of CDH1.