PMID: 

ACS Omega. 2019 Jul 31 ;4(7):12259-12270. Epub 2019 Jul 17. PMID: 31460342

Abstract Title: 

Anti-Alzheimer's Disease Activity of Bromophenols from a Red Alga,(Harvey) Yamada.

Abstract: 

(Harvey) Yamada is a red alga with a myriad of bromophenols accompanied by a diverse array of biological activities. The main purpose of the present study was to characterize the anti-Alzheimer's disease activity of bromophenols fromvia inhibition of cholinesterases (AChE and BChE),β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and glycogen synthase kinase-3β (GSK-3β). The results of enzyme inhibition assays demonstrated 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl) ether () as potent inhibitors of aforementioned enzymes. Among the tested bromophenols,showed multifold higher inhibition of all of the tested enzymes. Enzyme kinetics revealed different modes of inhibition, and in silico molecular docking simulation demonstrated the importance of the 7-OH group and bromine number for H-bond and halogen-bond interactions, respectively. Similarly,-at 20μM concentration showed more than 50% inhibition of self-induced Aβaggregation. These results suggest that bromophenols from, especially highly brominated (), may represent a novel class of anti-Alzheimer's disease drugs.

read more

PMID: 

Phytother Res. 2010 Oct ;24(10):1447-50. PMID: 20878692

Abstract Title: 

A new antitumor arabinopyranoside from Laurencia majuscula induces G2/M cell cycle arrest.

Abstract: 

A new arabinopyranoside was isolated from the alga Laurencia majuscula (Harvey) Lucas, collected from the Xisha Islands in the South China Sea. Its structure was elucidated as hexadecyl-1-O-α-L-arabinopyranoside by spectroscopic analysis. It was found that arabinopyranoside had significant antitumor activity in LOVO and Bel-7402 cell lines. Flow cytometric analysis showed that arabinopyranoside arrested the cell cycle in the G2/M phase. Western blotting demonstrated that the protein expression of CDK1 and cyclin A related to the G2/M phase decreased markedly with arabinopyranoside treatment, with slight changes in cyclin B1 expression. Taken together, the findings identify a potential new antitumor therapeutic arabinopyranoside isolated from red alga Laurencia majuscula.

read more

PMID: 

Saudi Pharm J. 2018 Jan ;26(1):44-52. Epub 2017 Nov 10. PMID: 29379332

Abstract Title: 

Antimicrobial, antioxidant and anticancer activities of,andextracts.

Abstract: 

The antimicrobial, antioxidant, and anticancer activities of ethanolic extract ofwere determined. The highest antibacterial activity; 23.40 ± 0.58 mm (00.98 µg/ml) and 22.60 ± 2.10 mm (03.90 µg/ml) were obtained againstbyand, respectively. However,showed excellent antibacterial activity against(21.7 ± 1.5 mm; 1.95 µg/ml),(21.7 ± 0.58 mm; 1.95 µg/ml),(20.7 ± 1.2 mm; 1.95 µg/ml) and(20.1 ± 1.2 mm; 3.9 µg/ml). Moreover, the highest antifungal activity; 24.7 ± 2.0 mm (0.98 µg/ml), 23.7 ± 1.5 mm (0.98 µg/ml), 23.6 ± 1.5 mm (0.98 µg/ml) was obtained byagainst,and, respectively. The algal extracts showed DPPH radical scavenging activity in a concentration-dependent manner with maximum scavenging activity (77.6%, IC = 5.59 µg/ml and 77.07%, IC = 14.3 µg/ml) was provided byand, respectively. Theantitumor activity revealed that the ICvalues ofwere 58.9, 115.0, 54.5, 59.0, 101.0, 101.0, and 97.6 µg/ml;were 55.2, 96.8, 104.0, 78.7, 117.0, 217.0, 169.0 µg/ml; andwere 115.0, 221.0, 225.0, 200.0, 338.0, 242.0, and 189.0 µg/ml; respectively against A-549 (Lung carcinoma), Caco-2 (Intestinal carcinoma), HCT-116 (Colon carcinoma), Hela (Cervical carcinoma), HEp-2 (Larynx carcinoma), HepG-2 (Hepatocellular carcinoma), and MCF-7 (Breast carcinoma) cell lines.

read more

PMID: 

Mar Drugs. 2018 Dec 13 ;16(12). Epub 2018 Dec 13. PMID: 30551628

Abstract Title: 

Pro-Apoptotic Activity of French PolynesianExtract on Human Osteosarcoma Cells.

Abstract: 

Recently, seaweeds and their extracts have attracted great interest in the pharmaceutical industry as a source of bioactive compounds. Studies have demonstrated the cytotoxic activity of macroalgae towards different types of cancer cell models, and their consumption has been suggested as a chemo-preventive agent against several cancers such as breast, cervix and colon cancers. Reports relevant to the chemical properties of brown algaesp. are limited and those accompanied to a comprehensive evaluation of the biological activity on osteosarcoma (OS) are non existent. In this report, we explored the chemical composition of French Polynesianextract (EPP) by spectrophotometric assays (total phenolic, flavonoid and tannin content, and antioxidant activity) and by gas chromatography-mass spectrometry (GC-MS) analysis, and provided EPP lipid and sterols profiles. Several compounds with relevant biological activity were also identified that suggest interesting pharmacological and health-protecting effects for EPP. Moreover, we demonstrated that EPP presents good anti-proliferative and pro-apoptotic activities against two OS cell lines, SaOS-2 and MNNG, with different cancer-related phenotypes. Finally, our data suggest that EPP might target different properties associated with cancer development and aggressiveness.

read more

PMID: 

Antioxidants (Basel). 2019 Dec 26 ;9(1). Epub 2019 Dec 26. PMID: 31887984

Abstract Title: 

Consumption of Terpenoids-RichExtract Attenuates Hyperglycemia, Insulin Resistance and Oxidative Stress, and Upregulates PPARγ in a Rat Model of Type 2 Diabetes.

Abstract: 

Seaweeds are rich in structurally diverse bioactive compounds with promising therapeutic effects. This study aimed to isolate and identify terpenes from the brown algaand to investigate its antidiabetic activity, pointing to the possible involvement of peroxisome proliferator-activated receptor (PPAR)γ. Type 2 diabetes was induced by feeding rats a high fat diet (HFD) for 4 weeks followed by injection of 35 mg/kg streptozotocin (STZ). The diabetic rats receivedextract (PPE; 50, 100 and 200 mg/kg) for 4 weeks and samples were collected for analyses. HFD/STZ-induced rats showed hyperglycemia, dyslipidemia, impaired glucose tolerance, decreased insulin, and increased HbA1c and HOMA-IR. PPE ameliorated hyperglycemia and dyslipidemia, and improved glucose tolerance and insulin sensitivity in diabetic rats. Treatment with PPE increased hepatic hexokinase activity and glycogen, suppressed glucose-6-phosphatase, fructose-1,6-biphosphatase, and glycogen phosphorylase, and attenuated oxidative stress, inflammation, and liver injury and lipid infiltration in HFD/STZ-induced rats. In addition, PPE boosted antioxidants and upregulated PPARγ gene and protein expression in the liver of diabetic rats. Phytochemical investigation resulted in the isolation of six terpenes from PPE and in silico analysis revealed their binding affinity toward PPARγ. In conclusion,-derived terpenes attenuated hyperglycemia, dyslipidemia, oxidative stress, and inflammation, and improved insulin sensitivity and carbohydrate metabolism in type 2 diabetic rats. These beneficial effects are mediated via PPARγ activation. However, further studies to explore the exact mechanisms underlying the antidiabetic effect of PPE are recommended.

read more

PMID: 

Int J Clin Exp Pathol. 2019 ;12(3):808-816. Epub 2019 Mar 1. PMID: 31933888

Abstract Title: 

Celastrol inhibits colon cancer cell proliferation by downregulating miR-21 and PI3K/AKT/GSK-3β pathway.

Abstract: 

Celastrol is a traditional Chinese medicine, that is derived from Tripterygium wilfordii. It has been proposed to offer anti-tumor potential. MicroRNAs also play important roles in tumorigenesis. However, the anti-tumor mechanism of Celastrol and whether miRNAs are involved in the process are still unknown. In the present study, MTT assay was used to test the IC50 of Celastrol and cell viability. PCNA, PI3K, Akt, GSK3β, phosphorylated Akt and GSK3β were measured by western blotting. Flow cytometry was introduced to detect the apoptosis. We found Celastrol inhibited colon cancer cell viability in a dose-dependent manner companied with PCNA downregulation. Apoptosis was induced by Celastrol. After Celastrol treatment, BCL-2 expression decreased while BAX increased and the Caspase-3 activity was induced. Simultaneously, miR-21 expression was reduced in Celastrol-treated colon cancer cells. miR-21 mimic overexpression could enhance the cell viability, inhibit the apoptosis, decrease BCL-2 expression, increase BAX and induce Caspase-3 activity to some extent which were reversed by Celastrol. In addition, the PI3K/AKT/GSK-3β pathway was activated by miR-21 mimic but partially arrested by extra-adding Celastrol. Thus, Celastrol may inhibit colon cancer cell proliferation by negatively regulating miR-21 and the PI3K/AKT/GSK-3β pathway.

read more

PMID: 

Cancer Med. 2020 Jan ;9(2):783-796. Epub 2019 Nov 26. PMID: 31957323

Abstract Title: 

Antitumor activity of celastrol by inhibition of proliferation, invasion, and migration in cholangiocarcinoma via PTEN/PI3K/Akt pathway.

Abstract: 

AIM: Cholangiocarcinoma is a malignant tumor originating from bile duct epithelium. Currently, the treatment strategy is very limited and the prognosis is poor. Recent studies reported celastrol exhibits antigrowth and antimetastasis properties in many tumors. Our study aimed to assess the anti-CCA effects of cholangiocarcinoma (CCA) and the mechanisms involved in it.METHODS: In this study, the long-term and short-term antiproliferation effects was determined using colony formation and Cell Counting Kit-8 (CCK-8) assays, respectively. Flow cytometry was performed to quantify apoptosis. Furthermore, wound healing and transwell assays were performed to determine the cell migration and invasion capabilities, respectively. To further find the mechanism involved in the celastrol-induced biological functions, LY204002, a PI3K/Akt signaling inhibitor, and an Akt-1 overexpression plasmid were employed to find whether PI3K/Akt pathway was involved in the celastrol-induced CCA cell inhibition. Additionally, short interfering RNA (siRNA) was also used to investigate the mechanism involved in the celastrol-induced PI3K/Akt signaling inhibition. Western blotting and immunofluorescence assays were also performed to detect the degree of relative proteins. Moreover, we validated the antiproliferation and antimetastasis effects of celastrol in vivo by constructing subcutaneous and lung metastasis nude mice models.RESULTS: We discovered that celastrol effectively induced apoptotic cell death and inhibited the capacity of migration and invasion in CCA cells. Further mechanistic study identified that celastrol regulated the PI3K/Akt signaling pathway, and the antitumor efficacy was likely due to the upregulation of PTEN, a negative regulator of PI3K/Akt. Blockage of PTEN abolished the celastrol-induced PI3K/Akt signaling inhibition. Additionally, in vivo experiments conformed celastrol inhibited the tumor growth and lung metastasis with no serious side effects.CONCLUSIONS: Overall, our study elucidated a mechanistic framework for the anti-CCA effects of celastrol via PTEN/PI3K/Akt pathway.

read more

PMID: 

Antioxidants (Basel). 2019 Dec 31 ;9(1). Epub 2019 Dec 31. PMID: 31906147

Abstract Title: 

Celastrol Inhibits Dopaminergic Neuronal Death of Parkinson's Disease through Activating Mitophagy.

Abstract: 

Parkinson's disease (PD) is a neurodegenerative disease, which is associated with mitochondrial dysfunction and abnormal protein accumulation. No treatment can stop or slow PD. Autophagy inhibits neuronal death by removing damaged mitochondria and abnormal protein aggregations. Celastrol is a triterpene with antioxidant and anti-inflammatory effects. Up until now, no reports have shown that celastrol improves PD motor symptoms. In this study, we used PD cell and mouse models to evaluate the therapeutic efficacy and mechanism of celastrol. In the substantia nigra, we found lower levels of autophagic activity in patients with sporadic PD as compared to healthy controls. In neurons, celastrol enhances autophagy, autophagosome biogenesis (Beclin 1↑, Ambra1↑, Vps34↑, Atg7↑, Atg12↑, and LC3-II↑), and mitophagy (PINK1↑, DJ-1↑, and LRRK2↓), and these might be associated with MPAK signaling pathways. In the PD cell model, celastrol reduces MPP-induced dopaminergic neuronal death, mitochondrial membrane depolarization, and ATP reduction. In the PD mouse model, celastrol suppresses motor symptoms and neurodegeneration in the substantia nigra and striatum and enhances mitophagy (PINK1↑ and DJ-1↑) in the striatum. Using MPPto induce mitochondrial damage in neurons, we found celastrol controls mitochondrial quality by sequestering impaired mitochondria into autophagosomes for degradation. This is the first report to show that celastrol exerts neuroprotection in PD by activating mitophagy to degrade impaired mitochondria and further inhibit dopaminergic neuronal apoptosis. Celastrol may help to prevent and treat PD.

read more

PMID: 

Antioxidants (Basel). 2020 Jan 1 ;9(1). Epub 2020 Jan 1. PMID: 31906396

Abstract Title: 

Melatonin Prevents Transforming Growth Factor-β1-Stimulated Transdifferentiation of Renal Interstitial Fibroblasts to Myofibroblasts by Suppressing Reactive Oxygen Species-Dependent Mechanisms.

Abstract: 

Accumulating evidence suggests that the pineal hormone melatonin displays protective effects against renal fibrosis, but the mechanisms remain poorly understood. Here, we investigate the effect of the pineal hormone on transdifferentiation of renal fibroblasts to myofibroblasts invoked by transforming growth factor-β1 (TGF-β1). Increased proliferation and activation of renal interstitial fibroblasts after TGF-β1 treatment were attenuated by melatonin pretreatment. Mechanistically, melatonin suppressed Smad2/3 phosphorylation and nuclear co-localization of their phosphorylated forms and Smad4 after TGF-β1 stimulation. In addition, increased phosphorylations of Akt, extracellular signal-regulated kinase 1/2, and p38 after TGF-β1 treatment were also suppressed by the hormone. These effects of melatonin were not affected by pharmacological and genetic inhibition of its membrane receptors. Furthermore, melatonin significantly reversed an increase of intracellular reactive oxygen species (ROS) and malondialdehyde levels, and a decrease of the reduced glutathione/oxidized glutathione ratio after TGF-β1 treatment. Finally, TGF-β1-induced proliferation and activation were also suppressed by N-acetylcysteine. Altogether, these findings suggest that the pineal hormone melatonin prevents TGF-β1-induced transdifferentiation of renal interstitial fibroblasts to myofibroblasts via inhibition of Smad and non-Smad signaling cadcades by inhibiting ROS-mediated mechanisms in its receptor-independent manner.

read more

PMID: 

Antioxidants (Basel). 2020 Jan 6 ;9(1). Epub 2020 Jan 6. PMID: 31935797

Abstract Title: 

Curcumin as a Therapeutic Option in Retinal Diseases.

Abstract: 

The retina is subjected to oxidative stress due to its high vascularization, long time light exposition and a high density of mitochondria. Oxidative stress can lead to pathological processes, like cell apoptosis, angiogenesis and inflammation ending in retinal pathologies. Curcumin, a major bioactive component obtained from the spice turmeric () rhizome has been used for centuries in Asian countries for cooking and for curing all kinds of diseases like dysentery, chest congestion and pain in general, due to its antioxidant effects. Curcumin prevents the formation of reactive oxygen species and so it is a good protective agent. Curcumin has shown also anti-inflammatory, and antitumor properties. Curcumin is a natural product, which can be a therapeutic option in a variety of retinal diseases due to its pleiotropic properties. Some drawbacks are its poor solubility, bioavailability and lack of stability at physiological conditions; which have been shown in curcumin skeptical publications. In this review, we provide some lights and shadows on curcumin administration on the major retinal pathologies.

read more