PMID: 

Cancer Med. 2019 Dec 31. Epub 2019 Dec 31. PMID: 31891230

Abstract Title: 

Combined treatment with N-acetylcysteine and gefitinib overcomes drug resistance to gefitinib in NSCLC cell line.

Abstract: 

We aimed to explore the molecular substrate underlying EGFR-TKI resistance and investigate the effects of N-acetylcysteine (NAC) on reversing EGFR-TKI resistance. In the current research, the effects of NAC in combination with gefitinib on reversing gefitinib resistance were examined using CCK-8 assay, combination index (CI) method, matrigel invasion assay, wound-healing assay, flow cytometry, western blot, and quantitative real-time PCR (qRT-PCR). CCK8 assay showed that NAC plus gefitinib combination overcame EGFR-TKI resistance in non-small cell lung cancer (NSCLC) cells by lowering the value of half maximal inhibitory concentration (IC50). CI calculations demonstrated a synergistic effect between the two drugs (CI 

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PMID: 

Nat Prod Bioprospect. 2019 Oct ;9(5):345-349. Epub 2019 Sep 19. PMID: 31538308

Abstract Title: 

Inhibitory Effect of Alpha-Mangostin to Dengue Virus Replication and Cytokines Expression in Human Peripheral Blood Mononuclear Cells.

Abstract: 

Massive pro-inflammatory cytokines production has been correlated with the pathogenesis of severe dengue disease. The active compound of mangosteen fruit pericarps,α-mangostin, has been commonly used as traditional medicine and dietary supplement. We examined the effect of α-mangostin against dengue virus (DENV) infection in human peripheral blood mononuclear cells (PBMC) by the measurement of virus titer and TNF-α and IFN-γ cytokines concentration post infection. Increasing concentration of α-mangostin inhibited virus replication and reduced inflammatory cytokines expression at 24- and 48-h post infection. Our results support the potential use of α-mangostin as anti-antiviral and anti-inflammatory therapies in the treatment of dengue.

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PMID: 

Front Pharmacol. 2019 ;10:1305. Epub 2019 Nov 13. PMID: 31798444

Abstract Title: 

Alpha-Mangostin Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice Partly Through Activating Adenosine 5'-Monophosphate-Activated Protein Kinase.

Abstract: 

Pulmonary fibrosis (PF) is a devastating interstitial lung disease and characterized by an abnormal accumulation of extracellular matrix (ECM). Nintedanib (NDN) and pirfenidone are two approved therapies for PF, but their potential side-effects have been reported. Recently, the use of natural supplements for PF is attracting attention. Alpha-mangostin (α-MG) is an active xanthone-type compound isolated from the nutritious fruit mangosteen.In the present study, the potential effect and underlying mechanism ofα-MG were evaluated in bleomycin (BLM)-induced PF and activated primary lung fibroblasts (PLFs).Histopathological changes and collagen deposition were analyzedhematoxylin-eosin staining and Masson staining, the expression of nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX4) involved in oxidative stress in lung tissues was analyzed by immunochemistry staining. The expressions ofα-smooth muscle actin (α-SMA), collagen I (Col I), p-adenosine 5'-monophosphate-activated protein kinase (AMPK)/AMPK, and NOX4 were detected by Western blot, immunofluorescence or RT-PCR, and effects of α-MG on cell viability were detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide.results demonstrated thatα-MG treatment (10 mg/kg/day) significantly ameliorated BLM-induced deposition of ECM in lung tissues. Moreover, α-MG could inhibit protein expressions of α-SMA and Col I as well as its mRNA levels. In addition, α-MG also significantly inhibited transforming growth factor-β1/Smad2/3 pathway andregulated the protein expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in lung tissues.results demonstrated thatα-MG significantly increased p-AMPK/AMPK but reduced the protein expression level of α-SMA and Col I as well as NOX4 in activated PLFs. Further study demonstrated that these improvement effects were significantly blocked by compound C.α-MG treatment significantly decreased oxidative stress in lungs partly by activating AMPK mediated signaling pathway in BLM-induced PF and activated PLFs and decreased the deposition of ECM. The present study provides pharmacological evidence to support therapeutic application of α-MG in the treatment of PF.

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PMID: 

Aging (Albany NY). 2019 Dec 6 ;11(23):11084-11110. Epub 2019 Dec 6. PMID: 31806859

Abstract Title: 

α-Mangostin remodels visceral adipose tissue inflammation to ameliorate age-related metabolic disorders in mice.

Abstract: 

Low-grade chronic adipose tissue inflammation contributes to the onset and development of aging-related insulin resistance and type 2 diabetes. In the current study,α-mangostin, a xanthone isolated from mangosteen (), was identified to ameliorate lipopolysaccharides-induced acute adipose tissue inflammation in mice, by reducing the expression of pro-inflammatory cytokines and chemokines. In a cohort of young (3 months) and old (18-20 months) mice,α-mangostin mitigated aging-associated adiposity, hyperlipidemia, and insulin resistance. Further study showed that α-mangostin alleviated aging-related adipose tissue inflammation by reducing macrophage content and shifting pro-inflammatory macrophage polarization. Moreover, α-mangostin protected the old mice against liver injury through suppressing the secretion of microRNA-155-5p from macrophages. The above results demonstrated that α-mangostin represents a new scaffold to alleviate adipose tissue inflammation, which might be a novel candidate to treat aging-related metabolic disorders.

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PMID: 

Chem Biodivers. 2019 Dec 3. Epub 2019 Dec 3. PMID: 31794156

Abstract Title: 

Review Xanthones and Cancer: From Natural Sources to Mechanisms of Action.

Abstract: 

Xanthones are a class of heterocyclic natural products that have been widely studied for their pharmacological potential. In fact, they have been serving as scaffolds for the design of derivatives focusing on drug development. One of the main study targets of xanthones is their anticancer activity. Several compounds belonging to this class have already demonstrated cytotoxic and antitumor effects, making it a promising group for further exploration. This review therefore focuses on recently-published studies, emphasizing their natural and synthetic sources and describing the main mechanisms of action responsible for the anticancer effect of promising xanthones.

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PMID: 

Biochem Biophys Rep. 2020 Mar ;21:100718. Epub 2019 Dec 10. PMID: 31886417

Abstract Title: 

Xanthones protects lead-induced chronic kidney disease (CKD) via activating Nrf-2 and modulating NF-kB, MAPK pathway.

Abstract: 

Xanthones from a tropical fruit ofL. is known to possess a wide spectrum of pharmacologic properties, including antioxidant, anti-bacterial, anti-inflammatory, and antidiabetic activities. The current study aimed to assess the possible protective effects of xanthones against lead acetate (PbAc)-induced chronic kidney disease (CKD). To accomplish,antioxidant assays of xanthones,oxidative stress parameters, histopathology, inflammatory parameters were evaluated using PbAc-induced IRC male mice. The study was supported bymolecular docking of respective organ receptor protein-ligand interaction. Results revealed that xanthones potentially scavenged the DPPH, superoxide, hydroxyl, and nitric oxide radicals. Oxidative stress, kidney dysfunction, inflammatory markers, and kidney apoptosis increased by PbAc were attenuated with the co-treatment of xanthones. The treatment remarkably improved the tissue architecture. Of note,prediction of activity study showed that protective role of xanthones could be due to its efficacy to activate the Nrf-2, regulate the intracellular [Ca], as well as downregulate the NF-kB, MAPK pathway. In a nutshell, xanthones could be a potential candidate for the management of PbAc-induced kidney damage.

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PMID: 

Cell Stress Chaperones. 2020 Jan 2. Epub 2020 Jan 2. PMID: 31898286

Abstract Title: 

α-Mangostin reduced the viability of A594 cells in vitro by provoking ROS production through downregulation of NAMPT/NAD.

Abstract: 

α-Mangostin (MAN) is a bioactive compound isolated from the inedible pericarp of a tropical fruit mangosteen (Garcinia mangostana Linn). It exhibits notable therapeutic potentials on lung cancers, but the underlying mechanisms are still largely unknown. This study was designed to further explore the mechanisms involved in cytotoxicity of MAN on A549 cells. Apoptosis and cell cycle distribution were analyzed by flow cytometry methods. The fluorescent probes DCFH-DA and JC-1 were used to assess the intracellular reactive oxidative species (ROS) and mitochondrial membrane potential statuses, respectively. The regulation of MAN on relevant pathways was investigated by immunoblotting assays. The results obtained indicated that MAN caused significant apoptosis and cell cycle arrest in A549 cells, which eventually resulted in inhibition on cell proliferation in vitro. All these phenomena weresynchronized with escalated oxidative stress and downregulation of nicotinamide phosphoribosyltransferase/nicotinamide adenine dinucleotide (NAMPT/NAD). Supplementation with nicotinamide mononucleotide (NMN) and N-acetylcysteine (NAC) efficiently eased MAN-induced ROS accumulation, and potently antagonized MAN-elicited apoptosis and cell cycle arrest. The pro-apoptotic effect of MAN was further confirmed by increased expressions of cleaved caspase 3, 6, 7, and 9, and its effect on cell cycle progression was validated by the altered expressions of p-p38, p-p53, CDK4, and cyclin D1. The immunoblotting assays also demonstrated that NAC/NMN effectively restored these molecular changes elicited by MAN treatment. Collectively, this study revealed a unique anti-tumor mechanism of MAN by provoking ROS production through downregulation of NAMPT/NAD signaling and further validated MAN as a potential therapeutic reagent for lung cancer treatment.

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PMID: 

Cureus. 2019 Nov 27 ;11(11):e6251. Epub 2019 Nov 27. PMID: 31890447

Abstract Title: 

Novel Use of N-Acetylcysteine in Management of Tyrosine Kinase Inhibitor Induced Acute Liver Injury.

Abstract: 

Tyrosine kinase inhibitors (TKIs) have been adopted in the treatment of a variety of malignancies. Despite their popularity, the underlying mechanism of the adverse effects seen with the use of TKIs is not completely understood. Acute liver injury is a known side effect of many of these drugs. Some papers have demonstrated that N-acetylcysteine may have a role in non-acetaminophen induced acute liver failure (NAI-ALF). There is little evidence supporting the use of N-acetylcysteine in the treatment of tyrosine kinase inhibitor-induced acute liver injury. This case report adds to the limited body of existing knowledge. We present a 67-year-old Caucasian female with a past medical history of anxiety, hyperlipidemia, in utero exposure to diethylstilbestrol (DES), and well-differentiated angiosarcoma of the right breast. She achieved remission for approximately six years after mastectomy with adjuvant chemotherapy and radiation. Subsequent surveillance imaging revealed new hepatic and cervical lesions. Further investigation with cutaneous biopsy near the occipital region confirmed recurrent metastatic angiosarcoma. The patient was started on high-dose pazopanib and initially tolerated the TKI without any adverse effects. However, after approximately two weeks of therapy, she began to experience dark colored urine, myalgias, and fatigue. These symptoms, along with significant elevations in liver enzymes (alanine transaminase of 1377 units/L, aspartate transaminase of 1212 units/L), prompted admission for evaluation of acute liver injury. The etiology of the acute liver injury was suspected to be secondary to TKI therapy. Treatment with intravenous N-acetylcysteine was initiated for non-acetaminophen induced acute liver failure (NAI-ALF) and resulted in a dramatic improvement in transaminases before discharge. Evidence suggests that there is a beneficial role for N-acetylcysteine in the management of NAI-ALF. However, when it comes specifically to the management of TKI induced acute liver injury, there is limited evidence to support its use. This case report highlights a possible use of N-acetylcysteine in the management of TKI mediated acute liver injury. Additional studies should be conducted to determine the role N-acetylcysteine plays in the management of TKI mediated liver injury.

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PMID: 

Zhongguo Yao Li Xue Bao. 1992 May ;13(3):209-12. PMID: 1442100

Abstract Title: 

Protective effects of fulvotomentosides on acetaminophen-induced hepatotoxicity.

Abstract: 

Fulvotomentosides (Ful) is the total saponins of Lonicera fulvotomentosa. In the present study, we examined the effect of Ful on acetaminophen (AA)-induced hepatotoxicity in mice. Ful pretreatment (75-225 mg.kg-1, sc x 3 d) significantly decreased AA (500 mg.kg-1, ip)-induced liver damage as indicated by serum activities of alanine aminotransferase and sorbitol dehydrogenase. Ful pretreatment (225 mg.kg-1, sc x 3 d) decreased hepatic cytochrome P-450, cytochrome b5, and NADPH-cytochrome c reductase by approximately 15-20%. Microsomes from Ful-pretreated mice, incubated in vitro with AA, produced less AA-glutathione. A 28% increase in urinary excretion of AA-glucuronide was observed in Ful (150 mg.kg-1, sc x 3 d) pretreated mice. Ful pretreatment had no influence on liver UDP-glucuronic acid concentration, but increased hepatic glucuronyltransferase activity towards AA. In summary, Ful pretreatment protects against AA-induced hepatotoxicity. One of the mechanisms for this protection appears to be the decreased AA toxic activation via P-450, as well as increased detoxication via glucuronidation of AA.

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PMID: 

Zhongguo Zhong Yao Za Zhi. 1999 Jun ;24(6):363-4, 384. PMID: 12212032

Abstract Title: 

[Hepatoprotective effect of several constituents of Lonicera fulvotomentosa hsu et S. C. cheng, and L. macranthoide Hand.-Mazz. on CC1(4) and D-galactosamine induced liver injuries in mice and rats].

Abstract: 

OBJECTIVE: To study the hepatoprotective effect of several constituents of Lonicera fulvotomentosa and L. macranthoide on CC1(4) and D-Galactosamine induced liver injury in mice and rats.METHOD: Mice and rats were given s.c. several constituents of L. fulvotomentosa and L. macranthoide, sGPT, hepatic triglycerides(TG) and malondialdehyde (MDA) were determined.RESULTS: All the compounds reduced the rise of sGPT and TG induced by CC1(4) and D-Galactosamine. Hepatic MDA formation caused by CC1(4) was also significantly decreased.CONCLUSION: Several constituents of L. fulvotomentosa and L. macranthoide are effective in decreasing CC1(4) and D-Galactosamine-induced liver injuries, and this effect appears to be due to the decrease of lipid peroxidation of CC1(4).

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