PMID: 

Avicenna J Phytomed. 2020 Jan-Feb;10(1):11-23. PMID: 31921604

Abstract Title: 

Molecular mechanisms underlying gallic acid effects against cardiovascular diseases: An update review.

Abstract: 

Objective: The prevalence of cardiovascular diseases (CVDs) is growing. CVDs are the major cause of mortality and have become one of the most important health challenges in developing countries. Gallic acid (GA) is a natural phytochemical which has been widely used against multiple conditions. The present review was designed to evaluate molecular mechanisms underlying the protective effects of this agent against CVDs.Materials and Methods: Data discussed in this review were collected from the articles published in databases such as Science Direct, Scopus, PubMed, and Scientific Information Database between 1993 and 2018.Results: According to the experimental studies, GA has protective actions against CVDs through increasing antioxidant enzymes capacity, inhibition of lipid peroxidation and decreasing serum levels of cardiac marker enzymes, modulation of hemodynamic parameters, recovery of electrocardiogram aberrations, and preservation of histopathological changes.Conclusion: GA has potential cardioprotective action. Therefore, it has been suggested that this agent can be administered in underlying of CVDS.

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PMID: 

Environ Toxicol. 2020 Jan 11. Epub 2020 Jan 11. PMID: 31925992

Abstract Title: 

Gallic acid prevents 1, 2-Dimethylhydrazine induced colon inflammation, toxicity, mucin depletion, and goblet cell disintegration.

Abstract: 

1,2-Dimethylhydrazine (DMH), an environmental toxicant specifically targets the colon. The present study was aimed to evaluate the efficacy of gallic acid (GA) against colon toxicity induced by DMH in Wistar rats. GA, a phenolic acid has numerous beneficial properties, which include antiviral, antifungal and antioxidant properties which help cells to overcome oxidative stress and balance the redox homeostasis. GA was administered orally at two doses (25 and 50 mg/kg body weight) once daily for 14 days and a single dose (40 mg/kg body weight) of DMH was administered subcutaneously on 14th day. Animals were sacrificed on the 15th day and we could find that GA at both the doses significantly ameliorates DMH-induced increased toxicity markers and alsosubstantially increases the glutathione content level and activities of detoxifying enzymes. It also ameliorates the expression of proliferation, inflammation, apoptosis, goblet cell disintegration, and mucin depletion in the colon that was elevated upon administration of DMH. Histological alterations provide further confirmation of the protective role of GA against DMH-induced colon toxicity. The results of this study clearly indicate supplementation of GA is beneficial in ameliorating DMH-induced oxidative stress, inflammation, proliferation, apoptosis, mucin depletion, and goblet cell disintegration in colon of Wistar rats.

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PMID: 

Sci Rep. 2020 Jan 29 ;10(1):1403. Epub 2020 Jan 29. PMID: 31996731

Abstract Title: 

Arctigenin inhibits prostate tumor growth in high-fat diet fed mice through dual actions on adipose tissue and tumor.

Abstract: 

This study investigated the inhibitory effect of arctigenin, a novel anti-inflammatory lignan, on prostate cancer in obese conditions both in vitro and in vivo. In vitro obese models were established by co-culture of mouse adipocytes 3T3-L1 with androgen-sensitive LNCaP human prostate cancer cells, or by culturing LNCaP cells in adipocytes-conditioned medium. Arctigenin significantly inhibited LNCaP proliferation, along with decreased androgen receptor (AR) and increased Nkx3.1 cellular expression. Male severe combined immunodeficiency mice were subcutaneously implanted with human prostate cancer LAPC-4 xenograft tumors for in vivo study. Mice were fed high-fat (HF) diet and orally given arctigenin at 50 mg/kg body weight daily or vehicle control for 6 weeks. Tumor bearing HF control mice showed a significant increase in serum free fatty acids (FFAs) and decrease in subcutaneous/peritoneal fat depots compared to non-tumor bearing control mice. Arctigenin intervention significantly reduced tumor growth by 45%, associated with decreased circulating FFAs and adipokines/cytokines including IGF-1, VEGF, and MCP-1, along with decreased AR, Ki67, and microvessel density and increased Nkx3.1 expression in tumors. These results indicate the strong ability of arctigenin to co-target obesity and tumoritself in inhibition of prostate tumor growth at a lower concentration compared to most phytochemicals.

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PMID: 

Mol Med Rep. 2020 Mar ;21(3):1374-1382. Epub 2020 Jan 13. PMID: 32016480

Abstract Title: 

Anti‑metastatic effects of arctigenin are regulated by MAPK/AP‑1 signaling in 4T‑1 mouse breast cancer cells.

Abstract: 

Arctigenin is a natural lignan that is found in burdock with anti‑viral, ‑oxidative, ‑inflammatory and anti‑tumor activities. In the current study, the effect of arctigenin on metastatic potential was examined in 4T‑1 mouse triple‑negative breast cancer cells. The results indicated that arctigenin inhibited cell motility and invasiveness, which was determined using wound healing and transwell invasion assays. Arctigenin suppressed matrix metalloprotease‑9 (MMP‑9) activity via gelatin zymography, and protein expression of cyclooxygenase‑2 (COX‑2) and MMP‑3. Furthermore, arctigenin attenuated the mRNA expression of metastatic factors,including MMP‑9, MMP‑3 and COX‑2. Based on these results, the effect of arctigenin on the mitogen‑activated protein kinase (MAPK)/activating protein‑1 (AP‑1) signaling pathway was assessed in an attempt to identify the regulatory mechanism responsible for its anti‑metastatic effects.Arctigenin was demonstrated to inhibit the phosphorylation of extracellular signal‑regulated protein kinase (ERK) and c‑Jun N‑terminal kinase (JNK), and the nuclear translocations of the AP‑1 subunits, c‑Jun and c‑Fos. In summary, the present study demonstrated that in 4T‑1 mouse triple‑negative breast cancer cells the anti‑metastatic effect of arctigenin is mediated by the inhibition of MMP‑9 activity and by the inhibition of the metastasis‑enhancing factors MMP‑9, MMP‑3 and COX‑2, due to the suppression of the MAPK/AP‑1 signaling pathway. The results of the current study demonstrated that arctigenin exhibits a potential for preventing cell migration and invasion in triple negative breast cancer.

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PMID: 

Saudi Pharm J. 2019 Nov ;27(7):1053-1060. Epub 2019 Sep 25. PMID: 31997913

Abstract Title: 

Evaluation of cytotoxicity, cell cycle arrest and apoptosis induced byLessential oil in human hepatocellular carcinoma cell line.

Abstract: 

L. () commonly known as, is an essential oil bearing plant extensively being used in traditional system of medicine. However, the reports on the components and biological responses ofessential oil (AG-EO) from Saudi Arabia are scarce. The present study was designed to explore the presence of basic constituents and apoptosis induced by AG-EO in HepG2 cells. The constituents in AG-EO was analyzed by Gas chromatography-Mass spectroscopy (GC-MS). Cytotoxicity of AG-EO was measured by MTT assay and cell cycle arrest and apoptosis assays were conducted by using flow cytometer. Based on GC-MS analysis, the main constituents present in AG-EO were carvone (53.130%), dillapole (25.420%), dihydrocarvone 2 (11.350%) and dihydrocarvone 1 (6.260%). A few other minor components were also identified-dihydrocarveol (0.690%), limonene (0.580%), isodihydrocarveol (0.370%), myristicin (0.210%) and-arsone (0.190%). The cytotoxicity results showed that AG-EO decrease the cell viability and inhibit the cell growth of HepG2 cells in a concentration-dependent manner. The inhibitory activity of AG-EO was found with IC = 59.6  5.64. The cell cycle arrest results showed that HepG2 cells exposed to AG-EO exhibited an increase in G2/M and pre-G1 cell population after 24 h exposure. Furthermore, the flow cytometry data revealed the primarily activation of cell death by apoptosis manners in HepG2 cells exposed to AG-EO. Overall, results from this study highlighted the anticancer potential of AG-EO, which could be considered as a new agent for the management of hepatocellular carcinoma.

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PMID: 

Mol Cell Biochem. 2020 Feb 17. Epub 2020 Feb 17. PMID: 32065351

Abstract Title: 

Arctigenin induces necroptosis through mitochondrial dysfunction with CCN1 upregulation in prostate cancer cells under lactic acidosis.

Abstract: 

Arctigenin, a mitochondrial complex I inhibitor, has been identified as a potential anti-tumor agent, but the involved mechanism still remains elusive. Herein, we studied the underlying mechanism(s) of action of arctigenin on acidity-tolerant prostate cancer PC-3AcT cells in the lactic acid-containing medium. At concentration showing no toxicity on normal prostate epithelial RWPE-1 and HPrEC cells, arctigenin alone or in combination with docetaxel induced significant cytotoxicity in PC-3AcT cells compared to parental PC-3 cells. With arctigenin treatment, reactive oxygen species (ROS) levels, annexin V-PE positive fractions, sub-G/Gpeak in cell cycle analysis, mitochondrial membrane depolarization, and cell communication network factor 1 (CCN1) levels were increased, while cellular ATP content and phospho (p)-Akt level were decreased. Pretreatment with ROS scavenger N-acetylcysteine effectively reversed the series of phenomena caused by arctigenin, suggesting that ROS served as upstream molecules of arctigenin-driven cytotoxicity. Meanwhile, arctigenin increased the levels of p-receptor-interacting serine/threonine-protein kinase 3 (p-RIP3) and p-mixed lineage kinase domain-like pseudokinase (p-MLKL) as necroptosis mediators, and pretreatment with necroptosis inhibitor necrostatin-1 restored their levels and cell viability. Treatment of spheroids with arctigenin resulted in necroptotic cell death, which was prevented by N-acetylcysteine. The siRNA-based knockdown of CCN1 suppressed the levels of MLKL, B-cell lymphoma 2 (Bcl-2), and induced myeloid leukemia cell differentiation (Mcl-1) with increased cleavage of Bcl-2-associated X (Bax) and caspase-3. Collectively, these results provide new insights into the molecular mechanisms underlying arctigenin-induced cytotoxicity, and support arctigenin as a potential therapeutic agent for targeting non-Warburg phenotype through induction of necroptosis via ROS-mediated mitochondrial damage and CCN1 upregulation.

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PMID: 

J Cell Mol Med. 2020 Feb 24. Epub 2020 Feb 24. PMID: 32090454

Abstract Title: 

Arctigenin prevents the progression of osteoarthritis by targeting PI3K/Akt/NF-κB axis: In vitro and in vivo studies.

Abstract: 

Osteoarthritis (OA), which is principally featured by progressive joint metabolic imbalance and subsequent degeneration of articular cartilage, is a common chronic joint disease. Arctigenin (ATG), a dietary phyto-oestrogen, has been described to have potent anti-inflammatory effects. Nevertheless, its protective effects on OA have not been clearly established. The target of our following study is to evaluate the protective effects of ATG on IL-1β-induced human OA chondrocytes and mouse OA model. Our results revealed that the ATG pre-treatment effectively decreases the level of pro-inflammatory mediators, such as prostaglandin E2 (PGE2), nitrous oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-6 and tumour necrosis factor alpha (TNF-α) in IL-1β-induced human chondrocytes. In addition, ATG protects against the degradation of extracellular matrix (ECM) under the stimulation of IL-1β and the possible mechanism might be connected with the inactivation of phosphatidylinositol-3-kinase (PI3K)/Akt/nuclearfactor-kappa B (NF-κB) axis. Furthermore, a powerful binding capacity between ATG and PI3K was also uncovered in our molecular docking research. Meanwhile, ATG may act as a protector on the mouse OA model. Collectively, all these findings suggest that ATG could be utilized as a promising therapeutic agent for the treatment of OA.

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PMID: 

Pharmacol Res. 2020 Feb 22:104721. Epub 2020 Feb 22. PMID: 32097750

Abstract Title: 

Arctigenin, a novel TMEM16A inhibitor for lung adenocarcinoma therapy.

Abstract: 

TMEM16A plays critical roles in physiological process and may serve as drug targets for diverse diseases. In recently, it has started to be regarded as potential primary lung adenocarcinoma targets. Here, we identified that arctigenin, a natural compound, is a novel TMEM16A inhibitor, and it can suppress lung adenocarcinoma growth through inhibiting TMEM16A both in vitro and in vivo. Our data also showed that the ICof actigenin to TMEM16A whole-cell current was 19.29 ± 4.69 μM, and the putative binding sites of arctigenin in TMEM16A were R515 and R535. Arctigenin concentration-dependently inhibited the proliferation and migration of LA795, however, the inhibition effect can be abolished by knockdown of the endogenous TMEM16A with shRNA. Further, we injected arctigenin on xenograft mouse model which exhibited significant antitumor activity with no adverse effect. At last, western blotting results showed the mechanism of arctigenin inhibiting lung adenocarcinoma was through inhibiting MAPK pathway. In summary, TMEM16A is a novel drug target for lungadenocarcinoma treatment. Arctigenin can be used as a lead compound for the development of lung adenocarcinoma therapy drugs.

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PMID: 

Int Immunopharmacol. 2020 Feb 18 ;82:106302. Epub 2020 Feb 18. PMID: 32086097

Abstract Title: 

Arctigenin ameliorates depression-like behaviors in Toxoplasma gondii-infected intermediate hosts via the TLR4/NF-κB and TNFR1/NF-κB signaling pathways.

Abstract: 

Toxoplasma gondii (T. gondii) is a known neurotropic protozoan that remains in the central nervous system and induces neuropsychiatric diseases in intermediate hosts. Arctigenin (AG) is one of the major bioactive lignans of the fruit Arctium lappa L. and has a broad spectrum of pharmacological activities such as neuroprotective, anti-inflammatory and anti-T. gondii effects. However, the effect of AG against depressive behaviors observed in T. gondii-infected hosts has not yet been clarified. In the present study, we analyzed the effects of AG against T. gondii-induced depressive behaviors in intermediate hosts using a microglia cell line (BV2 cells) and brain tissues of BALB/c mice during the acute phase of infection with the RH strain of T. gondii. AG attenuated microglial activation and neuroinflammation via the Toll-like receptor/nuclear factor-kappa B (NF-κB) and tumor necrosis factor receptor 1/NF-κB signaling pathways, followed by up-regulating the dopamine and 5-hydroxytryptamine levels and inhibiting the depression-like behaviors of hosts. AG also significantly decreased the T. gondii burden in mouse brain tissues. In conclusion, we elucidatedthe effects and underlying molecular mechanisms of AG against depressive behaviors induced by T. gondii infection.

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PMID: 

Postgrad Med J. 2020 Feb 3. Epub 2020 Feb 3. PMID: 32015189

Abstract Title: 

Acupuncture versus sham acupuncture for simple obesity: a systematic review and meta-analysis.

Abstract: 

Obesity is a growing chronic health problem worldwide. Studies about acupuncture for obesity treatment are many. But there are some doubts about the effectiveness of acupuncture versus sham acupuncture in treating obesity due to its lack of medical evidence. Therefore, the aim of this study is to assess the efficacy of acupuncture for obesity treatment and provide clinic evidence. Four English databases (PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials) and four Chinese databases (China National Knowledge Infrastructure, Chinese BioMedical Database, Chinese Scientific Journal Database and Wan-Fang Data) were searched from their receptions to August 2019. Randomized controlled trials (RCTs) using the comparison between acupuncture and sham acupuncture to treat simple obesity were included. The primary outcome of body mass index (BMI) would be used to measure the effect of acupuncture on obesity. According to the trial data extraction form based on the Cochrane Handbook, two reviewers separately extracted the data. Risk of bias of the RCTs was assessed by the Cochrane Risk of Bias Tool. The study included 8 RCTs with 403 patients. When compared with sham acupuncture, acupuncture showed obviously effect in BMI reduction (MD=1.0kg/m2, 95% CI=0.6 to 1.4, P

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