PMID: 

Cell Stress Chaperones. 2020 Mar 6. Epub 2020 Mar 6. PMID: 32144684

Abstract Title: 

Tanshinone IIA pretreatment promotes cell survival in human lung epithelial cells under hypoxia via AP-1-Nrf2 transcription factor.

Abstract: 

Activator protein-1 (AP-1) plays a decisive role in cell proliferation, apoptosis, and inflammation under hypoxia; thus, AP-1 subunits or dimers could be modulated for a desired phenomenon in a cell using a suitable compound of therapeutic potential. Herein, we used Tanshinone-IIA as an AP-1 (subunits) modulator, and the purpose of the study was to investigate the signaling mechanism exhibited by Tan-IIA in facilitating tolerance to hypoxia. A549 cells were pretreated with Tan-IIA and exposed to hypoxia for 6, 12, 24, and 48 h. Biochemical and molecular parameters were assessed in order to trace the signaling pathway. Tan-IIA attenuated hypoxia-induced oxidative stress by modulating the expression of AP-1 subunits (via. MAPK) and Nrf2 transcription factor, which in turn were responsible for maintaining the higher levels of antioxidant enzymes and genes (HO). Tan-IIA increased the cell survival. This could be attributed to an increased NO level via iNOS gene and activated JNK, ERK pathway that induced c-jun/c-fos, c-jun/fosB, junD/c-fos, and junD/fosB heterodimers. This in turn leads to the cell cycle progressionby activating cyclins (D and B). This was further confirmed by the lower levels of p53 and their downstream genes (p16, p21, p27). In addition, Tan-IIA decreased pro-inflammatory cytokine levels by inhibiting the formation of junB/fra-1 heterodimer regulated by p38. Tan-IIA increased cell survivalto hypoxia by maintaining the higher levels of cellular iNOS, HO-1, jun-D, c-jun, fos B via Nrf2-AP-1.

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PMID: 

Cytotechnology. 2020 Mar 11. Epub 2020 Mar 11. PMID: 32162175

Abstract Title: 

miR-497 plays a key role in Tanshinone IIA-attenuated proliferation in OCI-AML3 cells via the MAPK/ERK1/2 pathway.

Abstract: 

Acute myelod leukemia (AML), as a uncontrolled proliferation of cells, was arrested differentiation of progenitor cells. The present study aimed to explore Tanshinone IIA (TIIA) effects on OCI-AML3 and the involvement of the MAPK signaling pathway and miR-497 in TIIA-mediated effects. Cell growth percentage was detected using a cell counting kit. Expression of miR-497 was detected by qPCR. Phosphorylated ERK1/2, JNK and p38 were assessed using western blot. The growth percentage of OCI-AML3 decreased and the effected time increased with increasing TIIA concentration. The miR-497 was upregulated and the p-ERK1/2 was decreased when the TIIA added. TIIA cannot influence the p-ERK1/2. Hence, the proliferation of OCI-AML3 cells was raising. However, when the p-ERK1/2 was inhibited, there no influence on the miR-497 expression after TIIA added. TIIA upregulates miR-497, and decrease the p-ERK1/2 expression, when TIIA simulated OCI-AML3 cell in vitro. And in miR-497 might be involved in the regulation of proliferation in this process.

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PMID: 

Complement Ther Med. 2020 Mar ;49:102358. Epub 2020 Feb 26. PMID: 32147056

Abstract Title: 

The effects of pomegranate supplementation on biomarkers of inflammation and endothelial dysfunction: A meta-analysis and systematic review.

Abstract: 

OBJECTS: Cardiovascular disease (CVD) is one of the leading causes of death worldwide. CVD is associated with increased levels of reactive oxygen species which are pro-inflammatory and can damage the endothelium. The pomegranate fruit is a rich source of phytochemicals with a high antioxidant and anti-inflammatory activity, possessing thus health benefits. This systematic review and meta-analysis aims to evaluate the effect of pomegranate juice on the biomarkers of inflammation and vascular dysfunction.METHODS: Studies were identified using the PubMed/Medline and SCOPUS databases. Screening of relevant articles and references was carried out from inception until May 2019. This systematic review and meta-analysis was performed using the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses (PRISMA) guidelines.RESULTS: Overall, 16 randomized controlled trials (RCTs) involving 572 subjects were included in this study. Combining effect sizes from 16 studies, we recorded that pomegranate supplementation significantly reduced hs-CRP, IL-6 and TNF-α (Weighted Mean Diff ;erences (WMD): -6.57 mg/L, 95 % CI: -10.04 to -3.10, P = 0.000; WMD: -1.68 pg/mL, 95 % CI: -3.52, 0.157, P = 0.000; WMD: -2.37 pg/mL, 95 % CI: -3.67, -1.07, P = 0.00, respectively) levels, when compared to placebo. No significant reduction was found in CRP (WMD: 2.19 mg/dL,95 % CI: -3.28, 7.67, P = 0.61), E-selectin (WMD: 8.42 ng/mL, 95 % CI: -22.9, 39.8, P = 0.599), ICAM (WMD= -17.38 ng/mL, 95 % CI: -53.43, 18.66, P = 0.107), VCAM (WMD: -69.32 ng/mL, 95 % CI: -229.26, 90.61, P = 0.396) or MDA (WMD: 0.031 μmol/L, 95 % CI: -1.56, 0.218, P = 0.746) comparing pomegranate supplementation to placebo.CONCLUSION: We found a significant effect of pomegranate supplementation on hs-CRP, IL-6 and TNF-α in adults. However, the effects of pomegranate supplementation on CRP, E-selectin, ICAM, VCAM or MDA were not significant in this meta-analysis.

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PMID: 

Sci Rep. 2020 Mar 5 ;10(1):4075. Epub 2020 Mar 5. PMID: 32139811

Abstract Title: 

Effects of ayahuasca on mental health and quality of life in naïve users: A longitudinal and cross-sectional study combination.

Abstract: 

Ayahuasca is a hallucinogenic decoction used as a traditional medicine in several Amazonian regions. The ritualistic use of ayahuasca has spread throughout many countries, making it necessary to study its risks and benefits. Two sub-studies were designed for this investigation. In sub-study 1, a psychiatric interview and a battery of questionnaires were administered to subjects (n = 40) before their first ayahuasca use. Two follow-ups were conducted at 1 and 6 months. In sub-study 2, the same interview and battery of questionnaires were administered to long-term ayahuasca users (n = 23) and their scores were compared with those of the ayahuasca-naïve group. In the first assessment, nearly half (45%) of the naïve users were found to meet the diagnostic criteria for a psychiatric disorder. After the ayahuasca use, more than 80% of those subjects showed clinical improvements that persisted at 6 months. The questionnaires showed significant reductions in depression and psychopathology. Regarding sub-study 2, long-term users showed lower depression scores, and higher scores for self-transcendence and quality of life, as compared to their peers in sub-study 1. Further controlled and observational naturalistic studies assessing the eventual risks and potentialbenefits of ayahuasca are warranted.

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PMID: 

Biochem Pharmacol. 1993 Sep 14 ;46(6):1081-5. PMID: 8216352

Abstract Title: 

Preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats.

Abstract: 

The preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats was examined by histological and biochemical analysis. Acetaminophen at a dose of 750 mg/kg was administered to male Wistar rats with or without pretreatment with 50 mg/kg of gomisin A. Gomisin A inhibited not only the elevation of serum aminotransferase activity and hepatic lipoperoxides content, characteristic of acetaminophen administration, but also the appearance of histological changes such as degeneration and necrosis of hepatocytes. However, gomisin A did not affect the decrease in liver glutathione content. These results suggest that gomisin A protects the liver from injury after administration of acetaminophen through the suppression of lipid peroxidation.

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PMID: 

Arch Pharm Res. 2010 May ;33(5):697-701. Epub 2010 May 29. PMID: 20512467

Abstract Title: 

Anti-HIV-1 activity of lignans from the fruits of Schisandra rubriflora.

Abstract: 

This study investigated the 70% aqueous acetone extract of the fruits of Schisandra rubriflora which led to the isolation of eight lignans, including a new isolate, rubrisandrin C (1), and seven known lignans (2-8). The structure of 1 was established by extensive 1D and 2D NMR spectroscopy and its absolute stereochemistry was determined by CD spectrum. Compounds 1-5 and 7-8 were evaluated for their anti-HIV-1 activity that showed inhibitory activity on HIV-1(IIIB) induced syncytium formation with EC(50) values in the range of 2.26 approximately 20.4 microg/mL. Compounds 1 and 7 exerted their obvious protection of HIV-1(IIIB) inducted MT-4 host cells lytic effects with a selectivity index of 15.4 and 24.6, respectively.

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PMID: 

Int J Mol Med. 2013 Apr ;31(4):888-98. Epub 2013 Jan 31. PMID: 23381504

Abstract Title: 

Protective effects of gomisin A isolated from Schisandra chinensis against CCl(4)-induced hepatic and renal injury.

Abstract: 

The aim of the present study was to investigate the protective effects of gomisin A, a lignan compound isolated from Schisandra chinensis, against liver and kidney damage induced by CCl(4) exposure. We assessed alterations in organ weights, levels of serum biochemical indicators, and activation of the caspase-3 and MAPK signaling pathways and carried out histological analysis of liver and kidney tissue in rats pretreated with gomisin A for four days. In the gomisin A/CCl(4)-treated group, only the liver experienced a significant increase in weight, whereas the other organs did not undergo any changes. Five biochemical indicators in serum indicated that liver and kidney toxicity dramatically decreased upon gomisin A pretreatment, although the decrease in ratios varied. Upon histological analysis, the gomisin A/CCl(4)-treated group showed less hepatocellular necrosis, a poorly dilated central vein in the liver section, decreased diameter of the glomerulus, a lower number of capillaries, and a convoluted tubule in the kidney section. Furthermore, the formation of active caspase-3 was inhibited by gomisin A pretreatment in the gomisin A/CCl(4)-treated group, whereas the expression level of Bax protein was slightly increased. Western blot analysis revealed that there were differences between the liver and kidney in terms of activation of the MAPK signaling pathway. In the liver, gomisin A pretreatment increased phosphorylation of three members of the MAPK pathway when compared to that in the vehicle pretreatment group. However, in the kidney, only the phosphorylation level of p38 was elevated upon gomisin A pretreatment, whereas levels of the other two members were decreased. These results suggest that gomisin A induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway.

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PMID: 

J Asian Nat Prod Res. 2011 May ;13(5):393-9. PMID: 21534036

Abstract Title: 

Dibenzocyclooctadiene lignans from the fruits of Schisandra rubriflora and their anti-HIV-1 activities.

Abstract: 

Two new dibenzocyclooctadiene lignans, rubrilignans A and B (1, 2), together with 17 known ones, were isolated from the fruits of Schisandra rubriflora. The structures of 1 and 2 were elucidated by spectroscopic methods including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were also evaluated for their anti-HIV-1 activities and showed weak anti-HIV-1 activity with EC(50) values of 2.26 and 1.82μg/ml, and therapeutic index values of 35.5 and 18.6, respectively.

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PMID: 

Food Chem Toxicol. 2014 Jan ;63:119-27. Epub 2013 Nov 7. PMID: 24211520

Abstract Title: 

Gomisin A inhibits lipopolysaccharide-induced inflammatory responses in N9 microglia via blocking the NF-κB/MAPKs pathway.

Abstract: 

Gomisin A, one of the major dibenzocyclooctadiene lignans isolated from Schisandra chinensis Baill., has proved to possess a variety of pharmacological effects. The aim of the present study was to investigate the anti-inflammatory and neuroprotective effects of gomisin A as well as its potential molecular mechanisms. It was found that gomisin A not only inhibited the production of NO and PGE2 in a concentration-dependent manner but also suppressed the expressions of iNOS and COX-2 in LPS-stimulated N9 microglia without observable cytotoxicity. Gomisin A was also able to attenuate the mRNA expression and the production of pro-inflammatory factors TNF-α, IL-1β and IL-6. Moreover, LPS induced reactive oxygen species (ROS) production, NADPH oxidase activation, and gp91phox expression, which were markedly inhibited by gomisin A in microglia. Furthermore, the data showed that gomisin A significantly down-regulated the TLR4 protein expression, and inhibited nuclear transcription factor (NF)-κB and mitogen-activated protein kinases (MAPKs) signaling pathways. Additionally, gomisin A alleviated the cell death of SH-SY5Y neuroblastoma, rat primary cortical and hippocampal neurons induced by the conditioned-media from activated microglia. In summary, gomisin A may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways.

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PMID: 

Br J Pharmacol. 2017 04 ;174(8):672-688. Epub 2017 Mar 16. PMID: 28128437

Abstract Title: 

Schisandrol B protects against cholestatic liver injury through pregnane X receptors.

Abstract: 

BACKGROUND AND PURPOSE: Currently, ursodeoxycholic acid and obeticholic acid are the only two FDA-approved drugs for cholestatic liver diseases. Thus, new therapeutic approaches need to be developed. Here we have evaluated the anti-cholestasis effects of Schisandrol B (SolB), a bioactive compound isolated from Schisandra sphenanthera.EXPERIMENTAL APPROACH: Hepatoprotective effect of SolB against intrahepatic cholestasis, induced by lithocholic acid (LCA), was evaluated in mice. Metabolomic analysis and gene analysis were used to assess involvement of pregnane X receptor (PXR). Molecular docking, cell-based reporter gene analysis and knockout mice were used to demonstrate the critical role of the PXR pathway in the anti-cholestasis effects of SolB.KEY RESULTS: SolB protected against LCA-induced intrahepatic cholestasis. Furthermore, therapeutic treatment with SolB decreased mortality in cholestatic mice. Metabolomics and gene analysis showed that SolB accelerated metabolism of bile acids, promoted bile acid efflux into the intestine, and induced hepatic expression of the PXR-target genes Cyp3a11, Ugt1a1, and Oatp2, which are involved in bile acid homeostasis. Mechanistic studies showed that SolB activated human PXR and up-regulated PXR target genes in human cell lines. Additionally, SolB did not protect Pxr-null mice from liver injury induced by intrahepatic cholestasis, thus providing genetic evidence that the effect of SolB was PXR-dependent.CONCLUSION AND IMPLICATIONS: These findings provide direct evidence for the hepatoprotective effects of SolB against cholestasis by activating PXR. Therefore, SolB may provide a new and effective approach to the prevention and treatment of cholestatic liver diseases.

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