Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathway.

BACKGROUND: Jujuboside B (JuB) is the main bioactive saponin component of Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen, which has been reported to possess varied pharmacological functions. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of JuB on acetaminophen (APAP) overdose-induced hepatotoxicity have not been determined yet. METHODS: C57BL/6 J mice were pre-treated with JuB (20 or 40 mg/kg) for seven days before APAP (400 mg/kg) injection. After 24 h of APAP treatment, serum, and liver tissues were collected to evaluate the therapeutic effects. To investigate whether the Nrf2-STING signaling pathway is involved in the protective effects of JuB against APAP-induced hepatotoxicity, the mice received the DMXAA (the specific STING agonist) or ML385 (the specific Nrf2 inhibitor) during the administration of JuB, and Hematoxylin-eosin staining, Real-time PCR, immunohistochemical, and western blot were performed. RESULTS: JuB pretreatment reversed APAP-induced CYP2E1 accumulations and alleviated APAP-induced acute liver injury. Furthermore, JuB treatment significantly inhibited oxidative stress and the pro-inflammatory cytokines, as well as alleviated hepatocyte apoptosis induced by APAP. Besides, our result also demonstrated that JuB treatment upregulated the levels of total Nrf2, facilitated its nuclear translocation, upregulated the expression of HO-1 and NQO-1, and inhibited the APAP-induced STING pathway activation. Finally, we verified that the beneficial effects of JuB were weakened by DMXAA and ML385. CONCLUSION: Our study suggested that JuB could ameliorate APAP-induced hepatic damage and verified a previously unrecognized mechanism by which JuB prevented APAP-induced hepatotoxicity through adjusting the Nrf2-STING pathway.

Licochalcone B induces DNA damage, cell cycle arrest, apoptosis, and enhances TRAIL sensitivity in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a highly fatal disease recognized as a growing global health crisis. Traditional Chinese herbal medicines have been used to treat patients with cancer for many years in China. This study investigated the effects of licochalcone B (LCB), a flavonoid compound isolated from the root of Glycyrrhiza uralensis Fisch., on cell proliferation, DNA damage and TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in HCC cells. Our results showed that LCB inhibited cell proliferation and induced DNA damage, cell cycle arrest and apoptosis. Treatment with LCB significantly inhibited the Akt/mTOR pathway and activated endoplasmic reticulum (ER) stress and mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, combined treatment with LCB and TRAIL yielded evident enhancements in the viability reduction and apoptosis. LCB upregulated death receptor 4 (DR4) and death receptor 5 (DR5) protein in a concentration- and time-dependent manner. The knockdown of DR5 significantly suppressed TRAIL-induced cleavage of PARP, which was enhanced by LCB. Treatment with an extracellular-regulated kinase (ERK) inhibitor (PD98059) or c-Jun N-terminal kinase (JNK) inhibitor (SP600125) markedly reduced the LCB-induced upregulation of DR5 expression and attenuated LCB-mediated TRAIL sensitization. In summary, LCB exhibits cytotoxic activity through modulation of the Akt/mTOR, ER stress and MAPK pathways in HCC cells and effectively enhances TRAIL sensitivity through the upregulation of DR5 expression in ERK- and JNK-dependent manner. Combination therapy with LCB and TRAIL may be an alternative treatment strategy for HCC.

Cordycepin induces apoptosis in human pancreatic cancer cells via the mitochondrial-mediated intrinsic pathway and suppresses tumor growth in vivo.

BACKGROUND: Cordycepin, the main active ingredient of a traditional Chinese herbal remedy - extracted from Cordyceps sinensis - has been demonstrated as a very effective anti-inflammatory and antitumor drug. The present study investigated its antitumor effect on pancreatic cancer, a highly aggressive cancer with extremely poor prognosis due to malignancy, and clarified its underlying mechanism both in vitro and in vivo. METHODS: The antitumor viability of cordycepin on human pancreatic cancer MIAPaCa-2 and Capan-1 cells was determined by colony formation assays. Annexin V/PI double staining and flow cytometry assay were used to investigate whether cordycepin induced apoptosis and cell cycle arrest. The mitochondrial membrane potential (ΔΨm) was analyzed by Rhodamine 123 staining, and expression of related proteins evaluated by Western blot and immunohistochemistry, both on pancreatic cancer cells and tumor xenografts to reveal the potential mechanism for the effect of cordycepin. Furthermore, the in vivo efficacy was examined on nude mice bearing MIAPaCa-2 cell tumors treated by intraperitoneal injection of cordycepin (0, 15, and 50 mg/kg/d) for 28 days. RESULTS: Cordycepin inhibited cell viability, proliferation and colony formation ability and induced cell cycle arrest and early apoptosis of human pancreatic cancer cells (MIAPaCa-2 and Capan-1) in a dose- and time-dependent manner. The same effect was also observed in vivo. Decrease of ΔΨm and upregulation of Bax, cleaved caspase-3, cleaved caspase-9, and cleaved PARP as well as downregulation of Bcl-2 both in vitro and in vivo indicated that the mitochondria-mediated intrinsic pathway was involved in cordycepin's antitumor effect. CONCLUSION: Our data showed that cordycepin inhibited the activity of pancreatic cancer both in vitro and in vivo by regulating apoptosis-related protein expression through the mitochondrial pathway and suggest that cordycepin may be a promising therapeutic option for pancreatic cancer.

Bacillus capparidis sp. nov., an endophytic bacterium isolated from roots of Capparis spinosa L.

A novel endophytic bacterium, designated strain EGI 6500252T, was isolated from the surface-sterilized roots of a medicinal plant (Capparis spinosa L.) collected from Urumqi city, Xinjiang, north-west China. Cells were Gram-stain-positive, non-motile, aerobic, catalase- and oxidase-positive, rod-shaped and did not display spore formation. Strain EGI 6500252T grew at 10-40 °C (optimum 25-30 °C), at pH 6.0-8.0 (optimum pH 7.0) and in the presence of 0-10 % (w/v) NaCl (optimum 0-3 %). The major cellular fatty acids (>10 %) were identified as iso-C15 : 0, anteiso-C15 : 0, anteiso-C17 : 0 and summed feature 4. The predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, four unknown phospholipids, one unknown glycolipid and one unknown lipid. The dominant isoprenoid quinone was menaquinone 7 (MK-7). The DNA G+C content was 39.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain EGI 6500252T belonged to the genus Bacillus, and exhibited a highest 16S rRNA gene sequence similarity (96.2 %) that was lower than the suggested threshold (97.0 %) for separating bacterial species. On the basis of the phylogenetic analysis, chemotaxonomic data and physiological characteristics, strain EGI 6500252T represents a novel species of the genus Bacillus, for which the name Bacillus capparidis sp. nov. is proposed. The type strain is EGI 6500252T (=CGMCC 1.12820T=KCTC 33514T).

Marinactinospora endophytica sp. nov., isolated from a medicinal plant.

A novel endophytic actinobacterium, designated strain YIM 690053(T), was isolated from healthy stems of Salsola ferganica Drob, and was characterized using a polyphasic taxonomic approach. The strain formed well-branched substrate mycelia with no fragmentation, and abundant aerial mycelia that differentiated into long spores. The strain was found to grow at 10-55 °C, pH 6.0-10.0 and in the presence of 0-7 % (w/v) NaCl. The genomic DNA G+C content was determined to be 70.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM 690053(T) belongs to the genus Marinactinospora, and it shared the highest 16S rRNA gene sequence similarity with Marinactinospora thermotolerans SCSIO 00652(T) (98.96 %). However, the DNA-DNA relatedness values between the two strains was 37.85 ± 2.77 %. Based on the differences in the molecular and biochemical characteristics from its closest relative, strain YIM 690053(T) is concluded to represent a novel species of the genus Marinactinospora, for which the name Marinactinospora endophytica sp. nov. is proposed. The type strain is YIM 690053(T)(=KCTC 29664(T) = DSM 46799(T)).

[Create mathematical model and analysis of correlation between Chinese medicinal characteristics and immunoregulatory activity based on literature informatics].

OBJECTIVE: Intends to create mathematical model and analysis of correlation between Chinese medicinal characteristics and immunoregulatory activity based on literature informatics. METHOD: The numbers of the Chinese medicines with immune effects were worked out within the framework of "The China Pharmacopeia" of 2005 edition, from the literature publicized since 1980. The correlation and mathematical model were figured out between Chinese medicinal characteristics including biological classification, different tastes, channel tropism as well as the parts used and immunoregulatory activity based on the statistical software SPSS. RESULT: The results showed that the immunoregulatory activity was related to the five tastes of Chinese medicines, and the pungent medicines had less immune effect. The Chinese medicines of underground parts had more immune effect compared with other parts of the medicine. Medicines acting upon heart and kidneys were more powerful as for the immune effects (P <0.05). The coincidence was 74.7% between mathematical computing and original classification. CONCLUSION: There are correlations,between Chinese medicinal characteristics and immunoregulatory activity. The mathematical model based on these results can be used for immunopharmacology.