PMID: 

J Stroke Cerebrovasc Dis. 2019 Nov 11:104483. Epub 2019 Nov 11. PMID: 31727597

Abstract Title: 

Gastrodin Attenuates Neuronal Apoptosis and Neurological Deficits after Experimental Intracerebral Hemorrhage.

Abstract: 

OBJECTIVE: Gastrodin, a glucoside of gastrodigenin, inhibits cerebral oxidant stress and apoptosis in multiple central nervous system injury, but its effect in intracerebral hemorrhage (ICH) remains unclear. This study investigated the effect of gastrodin on neuronal apoptosis and neurological deficits in rat ICH model.METHODS: In vitro experiments were performed using hematoma lysate-induced cell damage model in primary cortical neurons. Rat ICH model was produced by a caudatum injection of collagenase. Gastrodin was intraperitoneal injected after 2 hours following ICH. Cell viability, brain water content, neurological score, western blot, and immunofluorescence experiments were performed.RESULTS: Gastrodin significantly decreased hematoma lysate-induced reduction of cell viability and cell apoptosis in primary cortical neurons. Gastrodin significantly improved brain edema and neurological deficits post-ICH. Moreover, gastrodin administration significantly reduced levels of ROS, 8-OHDG, 3-Nitrotyrosine and MDA, while increased GSH-Px and SOD activity, and stimulated the upregulation of Keap1, Nrf2, and HO-1 signaling at 72 hours post-ICH. Furthermore, gastrodin significantly increased Bcl-2 expression, while reduced level of Bax, active caspase-3 and active caspase-9, also reduced the number of active caspase-3 or TUNEL positive neurons at 72 hours post-ICH.CONCLUSION: These results suggest that gastrodin is neuroprotective after ICH and the mechanism may be associated with the inhibition of oxidative stress and neuronal apoptosis.

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PMID: 

Biomed Res Int. 2019 ;2019:5476076. Epub 2019 Aug 18. PMID: 31531357

Abstract Title: 

Study on the Effect of Ginsenosides Rb on Blood of Tumor Mice.

Abstract: 

Objective: The blood of cancer patients is in a state of hypercoagulability, easily leading to thrombosis. Anemia is also a complication of tumors. Anemia and thrombosis affect the treatment of tumor patients.Methods: Ginsenosides Rb were extracted from the stems and leaves of American ginseng using water-saturated ethanol and ethyl acetate in silica gel column. Tumor mice model was established by injecting Hhepatocellular carcinoma cells into the axilla of mice. Mice were randomly divided into 6 groups: normal control group, model control group, positive control group, low dose group (7 mg/kg), middle dose group (14 mg/kg), and high dose group (35 mg/kg). After 18 days, the blood was obtained by picking the eyeball of mice. The levels of red blood cells (RBC), hemoglobin (HGB), neutrophils/lymphocytes radio (NLR), platelets (PLT), platelet distribution width (PDW), fibrinogen (FIB), and D-Dimer (D-D) were measured and compared in each group of mice.Results: The content of obtained ginsenosides Rb reached 90.05%. This extraction process was simple and reliable. Middle dose of ginsenosides Rb could significantly increase RBC and HGB levels (P

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PMID: 

Nutr Cancer. 2019 Oct 12:1-12. Epub 2019 Oct 12. PMID: 31608663

Abstract Title: 

MicroRNAs mediate the anti-tumor and protective effects of ginsenosides.

Abstract: 

MicroRNAs (miRs(, as short non-coding RNAs, regulate important biological processes and mainly are associated with regulation of gene expression. The miRs are beneficial targets for diagnosis of various disorders, particularly cancer, since their expression profile undergoes alterations in pathological conditions. The numerous drugs have been designed with the capability of targeting miRs for treating pathological conditions. On the other hand, the application of naturally occurring compounds has been increased due to their minimal side effects and valuable biological and therapeutic activities. Ginsenosides are able to act as anti-tumor agents via either increasing or decreasing the expression level of miRs. Ginsenosides affect the expression profile of miRNAs to induce their protective impacts. Angiogenesis as a key factor in the progression of cancer can be suppressed by ginsenosides which is mediated by miR regulation. The aim of this review is to shed some light on the protective and anti-tumor activities of ginsenosides mediated by miRNAs.

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PMID: 

Curr Top Med Chem. 2019 Oct 17. Epub 2019 Oct 17. PMID: 31648643

Abstract Title: 

Recent Advances in Ginsenosides as Potential Therapeutics Against Breast Cancer.

Abstract: 

The dried root of ginseng (Panax ginseng C. A. Meyer or Panax quinquefolius L.) is a traditional Chinese medicine widely used to manage cancer symptoms and chemotherapy side effects in Asia. The anti-cancer efficacy of ginseng is attributed mainly to the presence of saponins, which are commonly known as ginsenosides. Ginsenosides were first identified as key active ingredients in Panax ginseng and subsequently found in Panax quinquefolius, both of the same genus. To review the recent advances on anti-cancer effects of ginsenosides against breast cancer, we conducted a literature study of scientific articles published from 2010 through 2018 to date by searching the major databases including Pubmed, SciFinder, Science Direct, Springer, Google Scholar, and CNKI. A total of 50 articles authored in either English or Chinese related to the anti-breast cancer activity of ginsenosides have been reviewed, and the in vitro, in vivo, and clinical studies on ginsenosides are summarized. This review focuses on how ginsenosides exert their anti-breast cancer activities through various mechanisms of action such as modulation of cell growth, modulation of cell cycle, modulation of cell death, inhibition of angiogenesis, inhibition of metastasis, inhibition of multidrug resistance, and cancer immune-modulation. In summary, recent advances in the evaluation of ginsenosides as therapeutic agents against breast cancer support further pre-clinical and clinical studies to treat primary and metastatic breast tumors.

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PMID: 

Integr Cancer Ther. 2019 Jan-Dec;18:1534735419886655. PMID: 31729239

Abstract Title: 

Functional Regulation of Ginsenosides on Myeloid Immunosuppressive Cells in the Tumor Microenvironment.

Abstract: 

Ginsenosides, the key components isolated from ginseng, have been extensively studied in antitumor treatment. Numerous studies have shown that ginsenosides have direct function in tumor cells through the induction of cancer cell apoptosis and the inhibition of cancer cell growth and enhance the antitumor immunity through the activation of cytotoxic T lymphocytes and natural killer cells. However, little is known about the function of ginsenosides on myeloid immunosuppressive cells including dendritic cells in tumor, tumor-associated macrophages, and myeloid-derived suppressor cells in the tumor microenvironments. Those myeloid immunosuppressive cells play important roles in promoting tumor angiogenesis, invasion, and metastasis. In the review, we summarize the regulatory functions of ginsenosides on myeloid immunosuppressive cells in tumor microenvironment, providing the novel therapeutic methods for clinical cancer treatment.

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PMID: 

Neurochem Res. 2019 Nov 14. Epub 2019 Nov 14. PMID: 31728857

Abstract Title: 

Paeoniflorin Alleviates HO-Induced Oxidative Injury Through Down-Regulation of MicroRNA-135a in HT-22 Cells.

Abstract: 

Paeoniflorin (PF) has been reported to possess neuroprotective influences on cognitive dysfunction illness. In current research, we attempted to probe into the protective influences of PF against HO-induced damage and the underlying regulating mechanisms on hippocampal HT-22 cells. HT-22 cells were pretreated with PF, and then induced by HO. Afterwards, the influences of PF pretreatment were examined using CCK-8 assay, apoptosis assay, western blot and ROS assay, respectively. In addition, the expression of microRNA-135a (miR-135a) was analyzed and altered by qRT-PCR and cell transfection, respectively. After overexpression of miR-135a, the effects of miR-135a mimic on cell functions were detected again. Moreover, influences of HO, PF and miR-135a overexpression on JAK2/STAT3 and ERK1/2 signal pathways were further investigated. Further experiments verified that PF pretreatment alleviated HO-induced oxidative stress through increasing cell viability, inhibiting cell apoptosis, reducing ROS generation and activating JAK2/STAT3 and ERK1/2 pathways. Besides, expression of miR-135a was declined by PF pretreatment. Whereas, miR-135a mimic abrogated the protective effects triggered by PF pretreatment. These results indicated that PF can alleviate HO-induced oxidative stress by down-regulation of miR-135a via activation of JAK2/STAT3 and ERK1/2 pathways.

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PMID: 

Mol Biol Rep. 2019 Oct 23. Epub 2019 Oct 23. PMID: 31646427

Abstract Title: 

Encapsulation of crocetin into poly (lactic-co-glycolic acid) nanoparticles overcomes drug resistance in human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS).

Abstract: 

Nanoparticles and herbal medicines have gained considerable attention in overcoming multidrug resistance through different mechanisms. In this study, the effects of poly (Lactic-co-glycolic acid)-crocetin nanoparticles (PLGA-Crt NPs) on MRPand MRPactivity in a human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS) and its parental form (A2780) were evaluated. PLGA-Crt NPs were formulated and then characterized. The cytotoxic effect of Crt, PLGA-Crt NPs, and empty PLGA NPs was assessed using MTT test in A2780 and A2780-RCIS cells. The effect of PLGA-Crt NPs on MRPand MRPmRNA expression was evaluated by Real-Time qRT-PCR. The impact of PLGA-Crt NPs on the functioning of MRP transporters was assessed by the doxorubicin efflux assay. The particle size, entrapment efficiency (EE) and loading capacity (LC) of PLGA-Crt NPs were obtained about 239.8 ± 9 nm, 79 ± 3% and 4.9 ± 0.2%, respectively. The PLGA-Crt NPs ICvalues were obtained 104 ± 3 µM and 96 ± 2 µM in A2780 and A2780-RCIS cell lines, respectively. The Real-time RT-PCR results demonstrated the inhibition of mRNA expression of MRPin all studied concentrations (up to 67 ± 8% at 100 µM) in A2780-RCIS cells. PLGA-Crt NPs showed more indirect efflux inhibition (up to 70 ± 5%) compared to direct inhibition (up to 49 ± 5%). The encapsulation of crocetin into PLGA NPs can increase its inhibitory effects on drug resistance by downregulating MRPtransporters.

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PMID: 

Inflammation. 2019 Oct 28. Epub 2019 Oct 28. PMID: 31659585

Abstract Title: 

The Association of Cigarette Smoke Exposure with Lung Cellular Toxicity and Oxidative Stress: the Protective Role of Crocin.

Abstract: 

Cigarette smoke (CS) contains many free radicals and toxic chemicals. Nuclear erythroid-related factor-2 (Nrf2) is a transcriptional regulator of several phase II antioxidant genes, including glutamate-cysteine ligase (GCL). In this study, it was hypothesized that Crocin may mediate antioxidant signaling pathway to protect human lung epithelial cells against CS-mediated toxicity and oxidative stress via inducing glutathione (GSH) biosynthesis and activation of Nrf2 pathway. Alveolar epithelial cells (A549) were exposed to 1, 2.5 and 5% cigarette smoke extracts (CSE) with or without Crocin (500 μM). After 48 h exposure, the cytotoxicity, oxidant/antioxidant parameters and the Nrf2 pathway modification were assayed. Treatment of A549 cells with all concentrations of CSE dose dependently decreased cell viability, antioxidant levels, GCL and Nrf2 gene expression, which was associated withincreased production of reactive oxygen species. Crocin not only restored CSE-depleted GSH levels by enhancing GCL expression via activation of Nrf2 but also quenched the CSE-generation and release of reactive oxygen species. Crocin attenuated CSE-mediated Nrf2 modifications, thereby inducing its nuclear accumulation associated with GCL gene transcription leading to enhanced GSH levels. By inducing GSH synthesis, Crocin attenuates CSE-mediated GSH depletion and protects cells against CSE-induced oxidative stress via Nrf2 pathway. These results may have implications in dietary modulation of natural antioxidants in treatment of pulmonary diseases.

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PMID: 

Pharmacol Rep. 2019 Jul 30 ;71(6):1228-1234. Epub 2019 Jul 30. PMID: 31670059

Abstract Title: 

Crocin protects cardiomyocytes against LPS-Induced inflammation.

Abstract: 

BACKGROUND: Sepsis causes organ dysfunctions via elevation of oxidative stress and inflammation. Lipopolysaccharide (LPS) is the major surface molecule of most gram-negative bacteria and routinely used as a sepsis model in investigation studies. Crocin is an active compound of saffron which has different pharmacological properties such as anti-oxidant and anti-inflammatory. In this research, the protective effect of crocin was evaluated against LPS-induced toxicity in the embryonic cardiomyocyte cell line (H9c2).METHODS: The cells were pre-treated with different concentration of crocin (10, 20 and 40μM) for 24 h, and then LPS was added (10 μg/ml) for another 24 h. Afterward, the percentage of cell viability and the levels of inflammatory cytokines (TNF-α, PGE, IL-1β, and IL-6), gene expression levels (TNF-α, COX-2, IL-1β, IL-6, and iNOS), and the level of nitric oxide (NO) and thiol were measured.RESULTS: Our results showed that LPS reduced cell viability, increased the levels of cytokines, gene-expression, nitric oxide, and thiol. Crocin attenuated the LPS-induced toxicity in H9c2 cells via reducing the levels of inflammatory factors (TNF-α, PGE, IL-1β, and IL-6, p 

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PMID: 

Int J Fertil Steril. 2020 Jan ;13(4):307-314. Epub 2019 Nov 11. PMID: 31710192

Abstract Title: 

Ameliorative Effect of Crocin on Sperm Parameters and In Vitro Fertilization in Mice under Oxidative Stress Induced by Paraquat.

Abstract: 

Background: Paraquat (PQ) is an herbicide that is genotoxic and cytotoxic for male germ cells. In this study, we investigated the protective role of crocin (Cr) against the destructive effects of PQ on sperm quality andfertilization (IVF) outcomes.Materials and Methods: In this experimental study, a total of 28 male mice (20-25 g) were divided into four groups: control, which received intraperitoneal (IP) injections of 0.1 ml normal saline per day; PQ group received IP injections of PQ (5 mg/kg/day); experimental (PQ+Cr group) received PQ along with IP injections of Cr (200 mg/kg/day); and positive control (Cr) received IP injections of Cr (200 mg/kg/day). In the last two weeks of the treatment period (35 days of treatment), 16 non-pregnant mice were stimulated to receive adult oocytes. At the end of the treatment period, after euthanizing the mice, the sperms were extracted from the epididymis of each mouse and prepared for evaluation of sperm parameters and IVF.Results: In the PQ+Cr group, Cr caused a significant increase in the average number of sperms and the mean percentage of motile and viable sperms. There was a significant decrease in the mean number of immature and DNA-damaged sperms compared to the PQ group (P

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