PMID: 

Cancers (Basel). 2020 Feb 12 ;12(2). Epub 2020 Feb 12. PMID: 32059469

Abstract Title: 

Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression.

Abstract: 

Reactive oxygen species (ROS) produced during intracellular metabolism or triggered by extrinsic factors can promote neoplastic transformation and malignant microenvironment that mediate tumor development. Oligo-Fucoidan is a sulfated polysaccharide isolated from the brown seaweed. Using human THP-1 monocytes and murine Raw264.7 macrophages as well as human HCT116 colorectal cancer cells, primary C6P2-L1 colorectal cancer cells and human MDA-MB231 breast cancer cells, we investigated the effect of Oligo-Fucoidan on inhibiting M2 macrophage differentiation and its therapeutic potential as a supplement in chemotherapy and tumor prevention. We now demonstrate that Oligo-Fucoidan is an antioxidant that suppresses intracellular ROS and mitochondrial superoxide levels in monocytes/macrophages and in aggressive cancer cells. Comparable to ROS inhibitors (DPI and NAC), Oligo-Fucoidan directly induced monocyte polarization toward M1-like macrophages and repolarized M2 macrophages into M1 phenotypes. DPI and Oligo-Fucoidan also cooperatively prevented M2 macrophage invasiveness. Indirectly, M1 polarity was advanced particularly when DPI suppressed ROS generation and supplemented with Oligo-Fucoidan in the cancer cells. Moreover, cisplatin chemoagent polarized monocytes and M0 macrophages toward M2-like phenotypes and Oligo-Fucoidan supplementation reduced these side effects. Furthermore, Oligo-Fucoidan promoted cytotoxicity of cisplatin and antagonized cisplatin effect on cancer cells to prevent M2 macrophage differentiation. More importantly, Oligo-Fucoidan inhibited tumor progression and M2 macrophage infiltration in tumor microenvironment, thus increasing of anti-tumor immunity.

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PMID: 

Int J Biol Macromol. 2020 Feb 15. Epub 2020 Feb 15. PMID: 32070744

Abstract Title: 

Fucoidan from Ecklonia maxima is a powerful inhibitor of the diabetes-related enzyme,α-glucosidase.

Abstract: 

Ecklonia maxima, an endemic South African seaweed, is a potential source of beneficial bioactive compounds. Among these compounds, fucoidan, a sulphated polysaccharide has a wide range of bioactivities including anti-diabetic activity. In this study, fucoidan was extracted from E. maxima by the hot water extraction method and then characterised by colorimetric assays for sugar composition. The extraction from E. maxima yielded 6.12% fucoidan which was found to contain 4.45 ± 0.25% L-fucose and 6.01 ± 0.53% sulphate. The water extracted E. maxima fucoidan had a low molecular weight of approximately 10-30 kDa. Structural studies (FT-IR, NMR and XRD) confirmed the structure and integrity of the fucoidan to be similar to previously studied fucoidans in literature. Finally, the activities of starch digestive enzymes; α-amylase and α-glucosidase, were investigated in the presence of the E. maxima fucoidan extract. Fucoidan from E. maxima was observed to be a potent mixed-type inhibitor of α-glucosidase with an ICrange of 0.27-0.31 mg/ml, which was significantly lower than the commercial anti-diabetic standard, acarbose. Our present study demonstrated that fucoidan from E. maxima is a more powerful inhibitor compared to some standard anti-diabetic compounds and thus shows great potential for managing type 2 diabetes.

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PMID: 

Comb Chem High Throughput Screen. 2020 Feb 19. Epub 2020 Feb 19. PMID: 32072893

Abstract Title: 

Favorable Effects of Astaxanthin on Brain Damage due to Ischemia-Reperfusion Injury.

Abstract: 

BACKGROUND: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect.OBJECTIVE: The aim of this study was to investigate the role of ASX on brain IRI.METHODS: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated.RESULTS: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p

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PMID: 

Front Pharmacol. 2019 ;10:1621. Epub 2020 Jan 30. PMID: 32082151

Abstract Title: 

Preventive and Therapeutic Effects of Astaxanthin on Depressive-Like Behaviors in High-Fat Diet and Streptozotocin-Treated Rats.

Abstract: 

The comorbidity of diabetes and depression has a negative impact on both lifestyle and quality of life. Astaxanthin (AST) has been demonstrated to improve glucose metabolism and has antidepressant-like effects, but it is not clear whether AST has potential for preventing depression in diabetes. The aim of this study is to observe the preventive and therapeutic effects of AST on glucose metabolism or depressive-like behaviors in a diabetic rat model produced by feeding with a high-fat diet for 10 weeks followed by injection of 25 mg/kg streptozotocin (STZ). Preventive treatment with AST at doses of 7.5, 15, and 25 mg/kg/day was given by intragastric gavage 4 weeks before STZ injection. Preventive plus therapeutic treatment also involved therapeutic AST treatments for 6 more weeks after STZ injection, whereas therapeutic-only treatment involved only the 6-week post-STZ treatment. Depressive-like behaviors were evaluated at the end of the treatment by using open field, locomotor activity, elevated plus maze, and forced swimming tests. Preventive and therapeutic treatment with AST both reduced the level of fasting glucose, improved glucose tolerance, and decreased total TCh and TG in diabetic rats. Preventive or preventative plus therapeutic treatment with AST decreased the immobility time and increased the time spent in the open arms of an elevated plus maze and locomotor activity in diabetic rats. However, therapeutic treatment with AST alone failed to affect the depressive-like behaviors. Preventive or preventative plus therapeutic treatment with AST at doses of 15 or 25 mg/kg significantly increased the expression of pERK, pAKT, pCREB, and BDNF in the prefrontal cortex (PFC) in diabetic rats. In contrast, therapeutic treatment with 25 mg/kg AST alone increased the expression of pERK in the PFC. This study indicates that AST may be used as a preventive or therapeutic approach for co-morbidity of diabetes and depression.

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PMID: 

Life Sci. 2020 Feb 19:117448. Epub 2020 Feb 19. PMID: 32087232

Abstract Title: 

Early astragaloside IV administration attenuates experimental autoimmune encephalomyelitis in mice by suppressing the maturation and function of dendritic cells.

Abstract: 

AIMS: Dendritic cells (DCs) actively participate in the pathogenesis of multiple sclerosis (MS), an autoimmune disease. Astragaloside IV (ASI), an active monomer isolated from the Chinese medicine Astragalus membranaceus, has a wide range of pharmacological effects. We aimed to elucidate the effects of ASI on the development of DCs in the early stage of MS/EAE.MAIN METHODS: The mice were administered with ASI (20 mg/kg) daily 3 days in advance of EAE induction and continuously until day 7 post-immunization. The effect of ASI on CD11cDC cells from bone marrow (BMDCs) or the spleen of EAE mice at day 7 post-immunization were investigated respectively by flow cytometry, elisa, western blot, real-time PCR and immunofluorescence.KEY FINDINGS: ASI administration in the early stage of EAE was demonstrated to delay the onset and alleviate the severity of the disease. ASI inhibited the maturation and the antigen presentation of DCs in spleen of EAE mice and LPS-stimulated BMDCs, as evidenced by decreased expressions of CD11c, CD86, CD40 and MHC II. Accordingly, DCs treated by ASI secreted less IL-6 and IL-12, and prevented the differentiation of CD4T cells into Th1 and Th17 cells, which was probably through inhibiting the activation of NFκB and MAPKs signaling pathways.SIGNIFICANCE: Our results implicated the alleviative effect of early ASI administration on EAE might be mediated by suppressing the maturation and function of DCs. The novel findings may add to our knowledge of ASI in the potentially clinical treatment of MS.

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PMID: 

Phytomedicine. 2020 Feb ;67:153162. Epub 2019 Dec 26. PMID: 31955134

Abstract Title: 

Regulation of serum lipidomics and amino acid profiles of rats with acute myocardial ischemia by Salvia miltiorrhiza and Panax notoginseng herb pair.

Abstract: 

BACKGROUND: Salvia miltiorrhiza and Panax notoginseng herb pair (DQ) has been widely used in traditional Chinese medicine for a long history to prevent and treat the coronary heart disease. However, its protective mechanisms against myocardial ischemia during coronary heart disease remain not well-understood.PURPOSE: In this study, we aimed to explore the protective mechanisms of DQ on myocardial ischemia from the perspective of serum lipidomics and amino acids (AAs).METHODS: Rats were orally administrated with low-dose DQ (L-DQ, 0.24 g/kg) and high-dose DQ (H-DQ, 0.96 g/kg) for two weeks and subcutaneously injected with isoproterenol (ISO, 65 mg/kg) for two consecutive days (13th and 14th days) to induce acute myocardial ischemia (AMI). Heart histopathology and serum biochemical indices were examined. The specifically altered serum lipid metabolites were profiled via lipidomics approach, while serum AA profiles were analyzed using UHPLC-TQ-MS/MS.RESULTS: Cardiac marker enzymes (CK, CK-MB, LDH and cTn-I) were significantly upregulated in AMI rats with some of which significantly dropped to normal level in L- and H-DQ groups. Serum TC, TG, HDL, LDL, VLDL and FFA were improved in AMI rats treatment with L- and H-DQ. Further, the PCA based on lipidomics showed serum lipid metabolites in L- and H-DQ groups were closer to control group than that in model group. Compared with model group, H-DQ pretreatment significantly reduced SM (d34:1) and CE (20:4), and increased FA (20:5), PC (26:1), TG (56:9), TG (54:7), MG (17:0), Cer (d32:0) and Cer (d34:0), whereas L-DQ significantly alleviated the perturbed levels of CE (20:4), FA (20:5), MG (17:0), and SM (d34:1). Moreover, there was a significant increment for leucine, isoleucine, valine, phenylalanine, lysine and glutamate but a significant reduction for tryptophan in the serum of rats in model group as compared to control group. Intriguingly, H-DQ could significantly decrease the levels of glutamate, lysine, isoleucine, and BCAAs (the sum of leucine, isoleucine and valine) after AMI, while L-DQ had no significant effects on the above altered AAs. The Western blotting results implied that H-DQ could promote the myocardial BCAA catabolism in AMI rats by activation of BCKDHA, whereas by inhibition of BCKDHK.CONCLUSION: This study presents evidence for the therapeutic effects of DQ on AMI injury, in part, via co-regulating lipid and AA metabolisms.

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PMID: 

Pharm Biol. 2020 Dec ;58(1):138-145. PMID: 31967924

Abstract Title: 

preparations as adjuvant therapy for diabetic kidney disease: a systematic review and meta-analysis.

Abstract: 

(Burk.) F.H. Chen (Araliaceae) preparations (PNP) are traditional Chinese medicines used as adjuvant therapeutics for diabetic kidney disease (DKD).To systematically review the efficacy of PNP as adjunct DKD therapy, including their effects on kidney function, serum lipid levels and fasting blood glucose levels.The databases PubMed, Embase, Medline, Cochrane Library, CINAHL, China Biology Medicine disc, Wanfang, VIP and China National Knowledge Infrastructure were systematically searched from the date of their inception until May 2019.,saponins, Lulutong, Xueshuantong and Xuesaitong were the key terms searched. Randomized controlled trials (RCTs) comparing the combined use of PNP and conventional medicines (CM) versus CM for DKD were included. Data were pooled using random or fixed effect models depending on heterogeneity.In total, 24 RCTs involving 1918 participants were analysed. Adjunct PNP with CM was associated with reduction of albuminuria (MD -26.89 mg, 95% CI: -33.35 to -20.42), proteinuria (MD -0.32 g/24 h, 95% CI: -0.36 to -0.27), serum creatinine (MD -4.52 μmol/L, 95% CI: -8.71 to -0.32), total cholesterol (MD -1.56 mmol/L, 95% CI: -2.33 to -0.78), triglycerides (TG) (MD -0.56 mmol/L, 95% CI: -0.80 to -0.31) and low-density lipoprotein cholesterol (MD -0.94 mmol/L, 95% CI: -1.49 to -0.40) compared with CM.This is the first meta-analysis investigating adjuvant PNP therapy for DKD. PNP apparently exerted beneficial effects on kidney function and improved the metabolism of serum lipids by CM. Further, well-conducted, high-quality trials on DKD patients are needed to provide high-quality evidence.

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PMID: 

Int J Biol Macromol. 2020 Feb 6 ;149:1084-1097. Epub 2020 Feb 6. PMID: 32035151

Abstract Title: 

A novel acidic polysaccharide from the residue of Panax notoginseng and its hepatoprotective effect on alcoholic liver damage in mice.

Abstract: 

This study presented the first purification and characterization of a hepatoprotective polysaccharide (PNPS-0.5 M) from the residue of Panax notoginseng (Burk.) F.H. Chen. This polysaccharide included a backbone of (4 → 1)-linked GalA and branches of (1→)-linked Araf, (1→)-linked Rhap, and (5 → 1)-linked Araf and had an extremely high molecular weight (2600 kDa). We investigated the hepatoprotective effects of PNPS-0.5 M on mice with alcoholic liver damage (ALD). After administration of PNPS-0.5 M, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and hepatic malondialdehyde (MDA) were reduced to normal. In contrast, hepatic levels of alcohol dehydrogenase (ADH) and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were elevated to normal. Further investigations indicated that PNPS-0.5 M activated Nrf2 signaling as a protective mechanism against Cyp2e1 toxicity in ALD mice. Meanwhile, it strengthened the ADH pathway and suppressed the CAT pathway of alcohol metabolism to prevent peroxide accumulation, thereby ameliorating ALD. In the present study, we describe a novel acidic polysaccharide from P. notoginseng with hepatoprotective activity that facilitates the development and utilization of P. notoginseng resources.

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PMID: 

J Ethnopharmacol. 2020 Jan 28 ;252:112637. Epub 2020 Jan 28. PMID: 32004631

Abstract Title: 

Astragalus propinquus Schischkin and Panax notoginseng (A&P) compound relieved cisplatin-induced acute kidney injury through inhibiting the mincle maintained macrophage inflammation.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Acute kidney injury (AKI) is a common disease in hospitalized patients, especially in critically ill patients. It is characterised with high morbidity and mortality, and is also an important cause of chronic kidney disease and chronic renal failure. Astragalus propinquus Schischkin and Panax notoginseng (A&P) compound, a famous traditional Chinese medicine, consists of Astragalus propinquus Schischkin, Panax notoginseng, Angelica sinensis, Achyranthes bidentata, and Ecklonia kurome, has been widely used for the treatment of various kidney diseases in the southwest of China. However, the effects of A&P on treatment of AKI and its underlying mechanism are needed to be uncovered.AIM OF THE STUDY: Recent researches reported that Mincle (Macrophage-inducible C-type lectin) plays a key role in renal injury of AKI by regulating the expression and secretion of inflammatory cytokines on macrophage through modulating NF-κB signaling pathway. Here, we aimed to investigate the renoprotective effect of A&P on AKI and whether by inhibiting Mincle.MATERIALS AND METHODS: We established a lipopolysaccharide (LPS)-induced Bone Marrow-Derived Macrophage (BMDM) inflammatory cell model and a cisplatin-induced mouse AKI model in vitro and in vivo. Renal histopathology staining was performed to observe kidney morphology. The expression and secretion of inflammatory cytokines were detected by real-time PCR and Enzyme-linked immunosorbent assay. Western blotting was used to detect the protein levels and Flow cytometry performed to detect polarization of macrophage.RESULTS: The results showed that A&P significantly reduced the mRNA expression of IL-1β, IL-6, TNFα and MCP-1 in LPS-stimulated BMDM cells, and secretion of IL-1β and IL-6 in supernatant. The same results were found in Cisplatin-induced AKI kidney and serum after treatment with A&P. The data also showed that A&P strongly reduced the mRNA and protein levels of Mincle in vitro and vivo, and also inhibited the activation of Syk and NF-κB. Notably, A&P down-regulated the M1 macrophage marker iNOS, which may relate to the inhibition of Mincle. Interestingly, both overexpression of Mincle by transfection of pcDNA3.1-Mincle plasmid and administration of TDB (a ligand of Mincle) can significantly abolished the A&P-inhibited inflammation in BMDM, suggesting Mincle pathway play a key role in macrophage inflammation in AKI.CONCLUSION: Our findings indicated that A&P protected kidney from inhibiting inflammation through down-regulating of Mincle pathway in macrophage in AKI. It provides a potential medicine compound for the treatment of AKI.

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PMID: 

BMC Complement Altern Med. 2018 Mar 9 ;18(1):83. Epub 2018 Mar 9. PMID: 29523109

Abstract Title: 

Extract from Astragalus membranaceus inhibit breast cancer cells proliferation via PI3K/AKT/mTOR signaling pathway.

Abstract: 

BACKGROUND: Astragalus membranaceus (AM) is a commonly used herb in traditional Chinese medicine (TCM), which has been used as an essential tonic to treat various diseases for more than 2000 years. In this study, we aimed to investigate the biological effects of extract from AM on breast cancer cell and its mechanism.
METHODS: To prepare the extract, dried AM were ground and extracted with water extraction-ethanol supernatant method. Then the main isoflavones in the extract was detect by HPLC analysis. Furthermore, the anti-proliferative activity of AM extract was examined by MTT assay and morphological observation. Cell apoptosis was evaluated with flow cytometric analysis. The expressions of total and phosphorylated PI3K, GS3Kβ, Akt and mTOR were determined by western blot analysis.
RESULTS: HPLC analysis demonstrated that AM extract contained with four kinds of isoflavones, campanulin, ononin, calycosin and formononetin. The MTT test and morphological observation indicated that cells proliferation of MCF-7, SK-BR-3 and MDA-MB-231were inhibited by AM extract in a dose dependent manner. Furthermore, flow cytometric analysis displayed that after treated with 25 μg/ml and 50 μg/ml AM extract, apoptosis of breast cancer cells was significantly increased as compared with DMSO and blank control group (all p < 0.05). Western blot analysis found that the level of p-PI3K, p-GS3Kβ, p-Akt, and p-mTOR were significantly decreased, but the level of total-mTOR was observably increased as compared with DMSO control group.
CONCLUSIONS: Taken together, the inhibited cell proliferation and induced cell apoptosis effect of AM extract via PI3K/AKT/mTOR pathway confirmed the anti-tumor potential of AM. Therefore, our findings provide a new insight into anti-cancer effect of AM extract as a promising agent in breast cancer treatment.