PMID: 

J Dermatolog Treat. 2019 Nov 21:1-5. Epub 2019 Nov 21. PMID: 31679408

Abstract Title: 

N-acetylcysteine versus chlorhexidine in treatment of aphthous ulcers: a preliminary clinical trial.

Abstract: 

This study sought to assess the efficacy of N-acetyl cysteine (NAC) in the treatment of recurrent aphthous stomatitis (RAS).Fifty-eight patients, aged 28 ± 9.7 years, presented with clinically diagnosed RAS to two oral medicine centers. They were assigned randomly to a single application of either NAC (200 mg dissolved in water, = 38) or 0.12% chlorhexidine digluconate (CHX, = 20) mouthwashes for 30 seconds. Pain was measured using a Visual Analog Scale (VAS). The size of the ulcer was measured through its greatest dimension using a periodontal probe. These two measurements were taken pre-application (day 1) and 2nd, 4th, and 6th day post-application. Average time (in days) until complete healing was assessed.Of all participants, 33 (57%) were females; 34 (59%) married; 29 (50%) reported a family history of aphthae; and 51 (88%) were affected with minor RAS. There were greater improvement in pain from day 1 with NAC on the second day (-3.0 ± 2.0 versus -1.8 ± 1.9; = .028) and on the fourth day (-5.0 ± 2.6 versus -3.4 ± 2.7; = .041). The differences with regard to the change in ulcer size and average healing time were not significant between NAC and CHX.Single application of NAC results in a clinically significant reduction of RAS-associated pain within one day of application and is more effective than CHX.

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PMID: 

Brain Res Bull. 2019 Nov 10. Epub 2019 Nov 10. PMID: 31722253

Abstract Title: 

Neuroprotective effects of N-acetylcysteine via inhibition of matrix metalloproteinase in a mouse model of transient global cerebral ischemia.

Abstract: 

N-acetylcysteine (NAC) is known to serve many biological functions including acting as an antioxidant, and electing antiinflammatory effects. Previous reports have revealed that NAC may have neuroprotective effects against the deleterious effects of brain ischemia. Despite of this, the mechanism by which NAC prevents neuronal damage after brain ischemia remains unclear. The current study aimed to investigate this mechanism in a mouse model of transient global brain ischemia. In the present study, mice were subjected to 20 min of transient global brain ischemia, proceeded by intraperitoneal administration of NAC (150 mg/kg) in one group. The mice were then euthanized 72 h after this ischemic insult for collection of experimental tissues. The effect of NAC on neuronal damage and matrix metalloproteinase (MMP)-9activity were assessed and immunofluorescence, and hippocampal terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay experiments were conducted and results compared between NAC- and vehicle-treated groups. Neuronal damage was primarily observed in the hippocampal CA1 and CA2 regions. In NAC-treated mice, neuronal damage was significantly reduced after ischemia when compared to vehicle-treated animals. NAC also inhibited increased MMP-9 activity after global brain ischemia. NAC increased laminin and NeuN expression and inhibited increases in TUNEL-positive cells, all in the hippocampus. These results suggest that NAC reduces hippocampal neuronal damage following transient global ischemia, potentially via reductions in MMP-9 activity.

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PMID: 

Neurochem Int. 2019 Nov 18:104602. Epub 2019 Nov 18. PMID: 31751619

Abstract Title: 

N-acetylcysteine (NAC) alleviates the peripheral neuropathy associated with liver cirrhosis via modulation of neural MEG3/PAR2/ NF-ҡB axis.

Abstract: 

BACKGROUND AND AIM: Oxidative stress (OS) is accused in pathogenesis of many diseases, including liver cirrhosis by many mechanisms. One of them is the disturbance of long non coding maternally expressed 3 (MEG3)/protease activated receptor 2 (PAR2) downstream pathway. We aimed to investigate the role of this axis in cirrhotic neuropathy and whether an antioxidant compound such as N-acetylcysteine (NAC) could improve the peripheral nerve function through repression of MEG3/PAR2.METHODS: Thirty Wistar rats were used and divided into 5 groups; naive, thiacetamide (TAA) (200 mg/kg 3 times/week. i.p. for 8 weeks) and TAA+NAC (50 or 100 or 200 mg/kg/day) groups. Von Frey (VF) test for mechanical nociceptive responses, hepatic&neural MEG3, NF-ҡB and neural PAR2 expression by PCR, histological studies for liver and sciatic nerve together with the dorsopedal skin thickness were done.RESULTS: TAA induced significant decrease in liver function, negative VF test, an increase in the expression of hepatic&neural MEG3, NF-ҡB and neural PAR2. The histological studies showed cirrhotic changes with atrophy of the sciatic nerve and the dorsal skin. NAC improved the liver function together with reversal of the neural: functional, biochemical and histological changes in a dose dependent manner.CONCLUSIONS: NAC could improve the peripheral neuropathy in cirrhotic rat through suppression of MEG3/PAR2 expression.

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PMID: 

Int J Mol Med. 2019 Oct ;44(4):1541-1551. Epub 2019 Jul 26. PMID: 31364719

Abstract Title: 

Artesunate alleviates interleukin‑1β‑induced inflammatory response and apoptosis by inhibiting the NF‑κB signaling pathway in chondrocyte‑like ATDC5 cells, and delays the progression of osteoarthritis in a mouse model.

Abstract: 

Osteoarthritis (OA) is a progressive and degenerative joint disorder that is highly prevalent worldwide and for which there is currently no effective medical therapy. Artesunate (ART), a natural compound used to treat malaria, possesses diverse biological properties, including the regulation of inflammation and apoptosis in various cells; however, its role in OA remains unclear. The aim of the present study was to investigate the effects of ART on interleukin (IL)‑1β‑induced chondrocyte‑like ATDC5 cells and in an OA mouse model. The results revealed that ART dose‑dependently relieved the inhibitory effect of IL‑1β on cell viability. Moreover, ART significantly reduced the overexpression of matrix metalloproteinase (MMP)‑3, MMP‑13, a disintegrin and metalloproteinase with thrombospondin motifs‑5 and cyclooxygenase‑2 at both the gene and protein levels in chondrocyte‑like ATDC5 cells stimulated by IL‑1β. Furthermore, ART decreased the expression of pro‑apoptotic Bax, cleaved caspase‑3 and cleaved caspase‑7 in a dose‑dependent manner, and increased the expression of the anti‑apoptotic factor Bcl‑2. These changes were mediated by the inhibitory effect of ART on the nuclear factor‑κB signaling pathway, defined as repression of the phosphorylation of IκBα and p65, and improved redistribution of p65. Additionally, ART blocked the advancement of the calcified cartilage zone and the loss of proteoglycan, and lowered histological scoring of OA in a mouse model. Taken together, these results indicate that ART may be of value as a therapeutic agent for OA.

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PMID: 

Int Immunopharmacol. 2019 Oct ;75:105817. Epub 2019 Aug 23. PMID: 31446161

Abstract Title: 

Artesunate alleviates imiquimod-induced psoriasis-like dermatitis in BALB/c mice.

Abstract: 

Artesunate (ART), a derivative of artemisinin, is a medication to treat malaria. Beyond that, the anti-inflammatory and immunoregulatory activities of ART have been identified in autoimmune diseases. However, whether ART functions in psoriasis-like dermatitis induced by imiquimod (IMQ, a TLR7/8 agonist) is currently unkown. There, we found that the cumulative score, epidermal thickening and expression of Ki-67 of ART-treated BALB/c mice were significantly lower than those in the IMQ psoriatic model group. In addition, ART treatment ameliorated mice from systemic inflammation. Mechanistically, ART reducedγδ T cells in draining lymph nodes, which might be benefit the improvement of dermatitis. These findings suggested that ART could be a promising drug of psoriasis in clinic.

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PMID: 

Drug Dev Res. 2019 Aug 30. Epub 2019 Aug 30. PMID: 31471932

Abstract Title: 

Artesunate suppresses inflammation and oxidative stress in a rat model of colorectal cancer.

Abstract: 

Anti-inflammatory drugs are well known to reduce the risk of colon cancer and prophylactic use of such agents is gaining acceptance as a cancer prevention therapy. As artesunate, an antimalarial drug, has been shown to exhibit chemopreventive properties, the present study was carried out to evaluate its inhibitory effect on oxidative stress and inflammation in a rat model of colon carcinogenesis. A chemical carcinogen, 1,2-dimethylhydrazine was injected twice at an interval of 1 week to induce preneoplastic lesions in the colon and the parameters indicating oxidative stress and inflammation were evaluated after 8 weeks. Artesunate (50 and 150 mg/kg) and aspirin (60 mg/kg) were administered orally throughout the study. Analysis of colon tissue revealed that both thedrugs preserved histoarchitecture, inhibited cellular influx, decreased the levels of oxidative stress and inflammatory markers, downregulated cyclooxygenase-2, inducible nitric oxide synthase, nuclear factor κB, and interleukin 1β in comparison to the experimental control. Suppression of oxidative stress and pro-inflammatory signaling by both the drugs were found to contribute to inhibition of colon carcinogenesis. The protection afforded by these drugs was found to be comparable. Our study shows that like aspirin, use of artesunate could also reduce the risk of colon cancer and it has a potential for further evaluation for the treatment purpose.

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PMID: 

Biochem Biophys Res Commun. 2019 Oct 29 ;519(1):41-45. Epub 2019 Aug 31. PMID: 31481232

Abstract Title: 

Artesunate promotes sensitivity to sorafenib in hepatocellular carcinoma.

Abstract: 

Enhancing sensitivity of carcinoma to sorafenib (Sor) is critical to overcome the limits of high frequency resistance and moderate efficiency during chemotherapy for advanced hepatocellular carcinoma (HCC). Here, we promote sensitivity of HCC to Sor by combination with Artesunate (Art), a derivative of artemisinin extracted from Chinese medical herb. The positive synergy of Art on inhibiting HCC growth contributes 48% dosage of Sor to reduce tumor cell viability in vitro and tumor size in vivo. Mechanically, in spite of effective suppression of RAF/MEK/ERK pathway, Sor is not able to eliminate chemoresistance of HCC driven by PI3K/AKT/mTOR pathway, while Art inhibits phosphorylation of AKT and mTOR significantly. Furthermore, combination with Art and Sor further improves apoptosis of HCC by dual inhibition of both pathways. Our study reveals a function of Art that induces HCC apoptosis via PI3K/AKT/mTOR pathway inhibition and suggests a potential therapeutic regimen of combination with Art and SOR against advanced HCC.

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PMID: 

Biochem Biophys Res Commun. 2019 Nov 12 ;519(3):533-539. Epub 2019 Sep 16. PMID: 31537387

Abstract Title: 

Artesunate activates the ATF4-CHOP-CHAC1 pathway and affects ferroptosis in Burkitt's Lymphoma.

Abstract: 

Currently, there is no effective treatment for Burkitt's lymphoma in patients aged above 60 years, and thus research on effective treatment options for Burkitt's lymphoma has been gaining increasing attention. Artesunate has been identified as a novel effective growth suppressor in Burkitt's lymphoma. Here, we utilized molecular biology, transcriptome analysis, and other techniques to study artesunate-induced death of the Burkitt's lymphoma cells DAUDI and CA-46, the effect of artesunate on gene expression in DAUDI and CA-46 cells, and the effect of artesunate-induced ATF4-CHOP-CHAC1 pathway on ferroptosis. We also studied the inhibitory effects and ferroptosis induction of artesunate on CA-46 cells in mouse xenografts. Results showed that artesunate induced ferroptosis in DAUDI and CA-46 cells, as evidenced by the protective effect of liproxstatin-1, ferrostatin-1, and desferoxamine, resulting in an endoplasmic reticulum stress response, activation of the ATF4-CHOP-CHAC1 pathway enhanced ferroptosis in DAUDI and CA-46 cells. A mouse-transplanted tumor model showed that artesunate can inhibit the proliferation and induce ferroptosis of CA-46 cells in vivo. This study provides a novel perspective for the development of drugs against different types of Burkitt's lymphomas.

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PMID: 

Recent Pat Anticancer Drug Discov. 2019 Oct 25. Epub 2019 Oct 25. PMID: 31746310

Abstract Title: 

Apigenin, A Plant Flavone Playing Noble Roles in Cancer Prevention Via Modulation of Key Cell Signaling Networks.

Abstract: 

BACKGROUND: Cancer is a global health problem and the continuous rise in incidence and mortality due to cancer carries a real economic burden to all countries. Accumulation of genetic mutation, exposure of environmental carcinogens and food habits due to change in lifestyles are the key reasons for cancer. Targeting cancer cells, we need a multitargeting molecule with low/no toxicity.OBJECTIVE: To review the current update of the research status of chemopreventive/therapeutic molecule, Apigenin.METHODS: Compare the results of the published articles and granted patents on this compound. We also discuss the pros and cons of the present research and future direction.RESULTS: Cancer cells have characteristic alterations and dysregulation of various cell signaling pathways that control cell homeostasis, proliferation, motility and survival in normal cells. Natural flavonoids are the compounds well known for their anti-inflammatory, anti-oxidant and anti-cancerous properties. Apigenin, along with several other physiological effects, has a very low intrinsic toxicity and striking effects on the proliferation of cancer cells. Interestingly, this multitargeting molecule is getting wide acceptance among researchers. It is evident from the recent patents filed in this compound. At present, three patents have been granted only on the anticancer properties of Apigenin.CONCLUSION: This mini-review will explain the present research status of Apigenin and will further throw some light on how Apigenin performs its anti-cancerous actions by interfering with the key cell-signaling pathways.

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PMID: 

Neurotoxicology. 2019 09 ;74:252-263. Epub 2019 Jul 27. PMID: 31362009

Abstract Title: 

Neuroprotection by luteolin and gallic acid against cobalt chloride-induced behavioural, morphological and neurochemical alterations in Wistar rats.

Abstract: 

Cobalt (Co) intoxication arising from occupational exposures and ion release from metal implants has been associated with neurological alterations such as cognitive decline, incoordination and depression. The present study evaluated the mechanisms of neuro-protection exerted by Luteolin (Lut; 100 mg/kg) and Gallic acid (GA; 120 mg/kg) in Wistar rats exposed to cobalt chloride (CoCl) at 150 mg/kg for 7 consecutive days. Results indicate that CoClinduced neuro-behavioural deficits specifically by decreasing exploratory activities of CoCl-exposed rats, increased anxiety, as well as significant reduction in hanging latency. Co-treatment with Lut or GA, however, restored these parameters to values near those of normal controls. Moreover, Lut and GA prevented CoCl-induced increases in hydrogen peroxide (HO), malondialdehyde (MDA) and nitric oxide (NO) in the brain, while also restoring the activities of acetylcholinesterase, glutathione S-transferase (GST) and superoxide dismutase (SOD). In addition, Lut and GA produced significant reversal of CoClinduced elevation in levels of serum Interleukin 1 beta (IL-1β) and Tumor necrosis factor (TNFα). Meanwhile, immunohistochemistry revealed increased astrocytic expression of glial fibrillary acidic protein (GFAP), with intense calbindin (CB) D-28k staining and pronounced dendrites in the Purkinje cells. In contrast, the CoClgroup was characterized by decreased number of neurons expressing CB and dendritic loss. Taken together, mechanisms of luteolin and/or gallic acid protection against Co toxicity involved restoration of Cahomeostasis, acetylcholinesterase and antioxidant enzyme activities, as well as inhibition of lipid peroxidation in the brain.

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