PMID: 

Int J Biol Macromol. 2020 Jan 20. Epub 2020 Jan 20. PMID: 31972198

Abstract Title: 

Gastric protective activities of fucoidan from brown alga Kjellmaniella crassifolia through the NF-κB signaling pathway.

Abstract: 

Fucoidan has been reported to have abundant biological activities. The objective of the present study was to detect the protective effects of fucoidan from Kjellmaniella crassifolia (KF) newly cultured in Dalian, North of China on aspirin-induced gastric ulcers of the Wistar rat model. The present study showed that inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 were effectively regulated in rats pretreated with KF. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities increased significantly in the KF pretreated groups, while the levels of maleic dialdehyde (MDA) decreased. The findings obtainedby RT-PCR and western blotting indicated that KF could suppress aspirin-induced NF-κB activation via stabilization of IκB-α and thereby induced the downregulation of COX-2 and iNOS. It was demonstrated that KF exerted positive gastric protective effects via suppression of the inflammatory response and oxidative stress, and the mechanism of KF appeared to mediate the NF-κB signaling pathway.

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PMID: 

J Clin Med. 2019 Dec 29 ;9(1). Epub 2019 Dec 29. PMID: 31905803

Abstract Title: 

Dietary Fucoxanthin Induces Anoikis in Colorectal Adenocarcinoma by Suppressing Integrin Signaling in a Murine Colorectal Cancer Model.

Abstract: 

Fucoxanthin (Fx), abundantly contained in edible brown algae, is a carotenoid with strong anti-cancer potential. Anoikis is an anchor-dependent apoptosis particularly related to integrin signaling, and a target for cancer preventive strategies. We recently demonstrated that Fx prevented colon cancer in azoxymethane-dextrane sodium sulfate (AOM/DSS) carcinogenic model mice, and that it increased anoikis-like integrinβ1/cleaved caspase-3cells in colonic mucosal crypts. However, an induction mechanism of anoikis by Fx in adenocarcinoma tissue remains unresolved. Thus, we investigated anoikis in colonic adenocarcinoma in AOM/DSS mice. Fx administration (30 mg/kg body weight) significantly suppressed the incidence and multiplicity of colonic adenocarcinoma in AOM/DSS mice. A number of anoikis-like integrinβ1/cleaved caspase-3cells in colonic adenocarcinoma and mucosal crypts were significantly increased, 8.3- and 3.5-fold in the Fx group compared with those of the control group, respectively. The results indicated the increase of anoikis-like cells occurred more strongly in colonic adenocarcinoma than in colonic mucosal crypts. In addition, integrinβ1 expression, and pFAK (Tyr) and pPaxillin (Tyr) activation in mucosal tissue decreased 0.7-, 0.5- and 0.6-fold by Fx administration, respectively. The results suggest that Fx induces anoikis in colonic adenocarcinoma developed by AOM/DSS treatment through attenuation of integrin signaling.

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PMID: 

Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Jan 10:158618. Epub 2020 Jan 10. PMID: 31931174

Abstract Title: 

Health benefits of fucoxanthin in the prevention of chronic diseases.

Abstract: 

Fucoxanthin is a xanthophyll carotenoid abundant in macroalgae, such as brown seaweeds. When fucoxanthin is consumed, it can be esterified or hydrolyzed to fucoxanthinol in the gastrointestinal tract and further converted into amarouciaxanthin A in the liver. It has a unique chemical structure that confers its biological effects. Fucoxanthin has a strong antioxidant capacity by scavenging singlet molecular oxygen and free radicals. Also, it exerts an anti-inflammatory effect. Studies have demonstrated potential health benefits of fucoxanthin for the prevention of chronic diseases, such as cancer, obesity, diabetes mellitus, and liver disease. Animal studies have shown that fucoxanthin supplementation has no adverse effects. However, investigation of the safety of fucoxanthin consumption in humans is lacking. Clinical trials are required to assess the safety of fucoxanthin in conjunction with the study of mechanisms by which fucoxanthin exhibits its health benefits. This review focuses on current knowledge of metabolism and functions of fucoxanthin with its potential health benefits. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

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PMID: 

Mol Biol Rep. 2020 Feb ;47(2):1161-1171. Epub 2019 Dec 9. PMID: 31820315

Abstract Title: 

Chlorogenic acid prevents hepatotoxicity in arsenic-treated mice: role of oxidative stress and apoptosis.

Abstract: 

Arsenic is a potent and toxic heavy metal found in the environment that causes health problems, including liver disease, in humans and animals. Chlorogenic acid (CA) is the most abundant caffeoylquinic acid isomer present in plants. This study aims to assess how CA protects the liver tissue following sodium arsenite (NaAsO)-induced toxicity in mice. Male Swiss mice were allocated into 5 groups: Control, intragastrically administered CA (200 mg/kg), intragastrically administered NaAsO(5 mg/kg), and two groups administered with CA (100 and 200 mg/kg) and NaAsO. CA was administered 30 min before NaAsOand all the mice were treated daily for 28 days. To investigate the biochemical, histopathological, immunohistochemical, and molecular changes, blood and liver samples were collected. NaAsOtreatment increased the liver function biomarkers such as alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin. Lipid and nitric oxide production was elevated. Glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase decreased, indicating a disturbance in redox homeostasis. Histopathological examination revealed a granular degeneration of hepatocytes, infiltration of inflammatory cells, and centrilobular hepatocyte necrosis. Furthermore, tumor necrosis factor-α and interleukin-1β were upregulated upon NaAsOtreatment, suggesting the induction of inflammation. Moreover, NaAsOtriggered apoptosis in the liver by upregulating Bax and caspase-3 and downregulating Bcl-2. However, CA abrogated the biochemical, molecular, and histological changes, reflecting its hepatoprotective role in response to NaAsOtreatment. Our findings demonstrate that CA could be a potential therapeutic to minimize NaAsO-induced hepatic injury.

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PMID: 

J Nat Prod. 2019 Apr 26 ;82(4):765-773. Epub 2019 Feb 18. PMID: 30776236

Abstract Title: 

Cytotoxic Withanolides from the Roots of Indian Ginseng ( Withania somnifera).

Abstract: 

Withania somnifera, commonly known as"Indian ginseng"or"ashwagandha", is popular as a functional food because of its diverse purported therapeutic efficacies including invigorating, improvement of cognitive ability, and stress release activities. Chemical investigation of the MeOH extract of W. somnifera roots combined with LC/MS-based analysis resulted in the identification of six new withanolides, withasilolides A-F (1-6), as well as seven known compounds (7-13). The structures of the new compounds were established by application of spectroscopic methods, including 1D and 2D NMR, HRMS, and ECD measurements. The cytotoxicity of the isolated compounds was evaluated against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15). Compounds 1, 2, 4, 6, and withanone (11) each showed cytotoxicity for one or more of the four cancer cell lines used.

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PMID: 

Cancers (Basel). 2019 Jul 17 ;11(7). Epub 2019 Jul 17. PMID: 31319622

Abstract Title: 

Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer.

Abstract: 

Low response rate and recurrence are common issues in lung cancer; thus, identifying a potential compound for these patients is essential. Utilizing an in silico screening method, we identified withaferin A (WA), a cell-permeable steroidal lactone initially extracted from, as a potential anti-lung cancer and anti-lung cancer stem-like cell (CSC) agent. First, we demonstrated that WA exhibited potent cytotoxicity in several lung cancer cells, as evidenced by low ICvalues. WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects. The increase in p62 indicated that WA may modulate the autophagy flux followed by apoptosis.research also demonstrated the anti-tumor effect of WA treatment. We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity, at least through downregulation of mTOR/STAT3 signaling. Furthermore, the combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability. In addition, WA can further enhance the cytotoxic effect of cisplatin in lung CSCs. Therefore, WA alone or in combination with standard chemotherapy is a potential treatment option for EGFR wild-type lung cancer and may decrease the occurrence of cisplatin resistance by inhibiting lung CSCs.

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PMID: 

Cell Prolif. 2020 Jan ;53(1):e12706. Epub 2019 Oct 23. PMID: 31642559

Abstract Title: 

Withaferin A triggers G2/M arrest and intrinsic apoptosis in glioblastoma cells via ATF4-ATF3-CHOP axis.

Abstract: 

OBJECTIVE: Withaferin A (WA) is a bioactive compound with a remarkable anti-cancer effect derived from Withania somnifera, commonly known as ashwagandha. However, the anti-cancer mechanisms of WA in glioblastoma multiforme (GBM) are still unclear.MATERIALS AND METHODS: Cell viability assays and xenografted nude mice were used to evaluate the effects of WA, along with flow cytometry to detect apoptosis and cell cycle of GBM. RNA-seq analysis, Western blotting, immunofluorescence staining, qRT-PCR and siRNA gene silencing were carried out to determine the signalling pathways affected by WA.RESULTS: Withaferin A significantly inhibited the growth of GBM in vitro and in vivo and triggered the intrinsic apoptosis of GBM cells by up-regulating expression of Bim and Bad. WA arrested GBM cells at the G2/M phase of the cell cycle through dephosphorylating Throf CDK1 by activating p53-independent p21 up-regulation. Knockdown of p21 restored cell cycle progression and cell viability by down-regulating the expression of Bad rather than Bim. We demonstrated that endoplasmic reticulum (ER) stress induced by WA through the ATF4-ATF3-CHOP axis, initiated apoptosis and G2/M arrest in GBM cells.CONCLUSION: We revealed a novel pathway that elucidated WA activation of apoptosis and G2/M arrest in GBM cells through the ATF4-ATF3-CHOP axis. This discovery is important for optimization of WA-based regimens for prevention and/or treatment of GBM.

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PMID: 

Cureus. 2019 Sep 28 ;11(9):e5797. Epub 2019 Sep 28. PMID: 31728244

Abstract Title: 

Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety: A Double-blind, Randomized, Placebo-controlled Study.

Abstract: 

Introduction Insomnia is a prevalent sleep disorder that can profoundly impact a person's physical health and mental wellbeing. Most of the currently available drugs for insomnia exert adverse effects. Hence, alternative herbal therapies could be effective in treating insomnia. Ashwagandha, a proven"Rasayana"from ancient Ayurveda is having the required potential to treat insomnia. Objective To determine the efficacy and safety of Ashwagandha root extract in patients with insomnia and anxiety. Methods This was a randomized, double-blind, placebo-controlled study conducted at Prakruti Hospital, Kalwa, Maharashtra, India. A total of 60 patients were randomly divided into two groups: test (n = 40) and placebo (n = 20) in a randomization ratio of 2:1. Test product was a capsule containing highest concentration full-spectrum Ashwagandha root extract 300 mg, and the placebo was an identical capsule containing starch. Both treatments were given twice daily with milk or water for 10 weeks. Sleep actigraphy (Respironics Philips) was used for assessment of sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE) and wake after sleep onset (WASO). Other assessments were total time in bed (sleep log), mental alertness on rising, sleep quality, Pittsburgh Sleep Quality Index (PSQI), and Hamilton Anxiety Rating Scale (HAM-A) scales. Results Two patients, one from each group, did not complete study and the per-protocol dataset (n = 58) included 29 and 19 patients from test and placebo, respectively. The baseline parameters were similar in the two groups at baseline. The sleep onset latency was improved in both test and placebo at five and 10 weeks. However, the SOL was significantly shorter (p, 0.019) after 10 weeks with test [29.00 (7.14)] compared to placebo [33.94 (7.65)]. Also, significant improvement in SE scores was observed with Ashwagandha which was 75.63 (2.70) for test at the baseline and increased to 83.48 (2.83) after 10 weeks, whereas for placebo the SE scores changed from 75.14 (3.73) at baseline to 79.68 (3.59) after 10 weeks. Similarly, significant improvement in sleepquality was observed with test compared to placebo (p, 0.002). Significant improvement was observed in all other sleep parameters, i.e., SOL, SE, PSQI and anxiety (HAM-A scores) with Ashwagandha root extract treatment for 10 weeks. Conclusion Ashwagandha root extract is a natural compound with sleep-inducing potential, well tolerated and improves sleep quality and sleep onset latency in patients with insomnia at a dose of 300 mg extract twice daily. It could be of potential use to improve sleep parameters in patients with insomnia and anxiety, but need further large-scale studies.

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PMID: 

Int J Mol Sci. 2019 Oct 25 ;20(21). Epub 2019 Oct 25. PMID: 31731424

Abstract Title: 

(Ashwagandha) and Withaferin A: Potential in Integrative Oncology.

Abstract: 

Ashwagandha (, belonging to the family Solanaceae, is an Ayurvedic herb known worldwide for its numerous beneficial health activities since ancient times. This medicinal plant provides benefits against many human illnesses such as epilepsy, depression, arthritis, diabetes, and palliative effects such as analgesic, rejuvenating, regenerating, and growth-promoting effects. Several clinical trials of the different parts of the herb have demonstrated safety in patients suffering from these diseases. In the last two decades, an active component of Withaferin A (WFA) has shown tremendous cytotoxic activity suggesting its potential as an anti-carcinogenic agent in treatment of several cancers. In spite of enormous progress, a thorough elaboration of the proposed mechanism and mode of action is absent. Herein, we provide a comprehensive review of the properties ofextracts (E) containing complex mixtures of diverse components including WFA, which have shown inhibitory properties against many cancers, (breast, colon, prostate, colon, ovarian, lung, brain), along with their mechanism of actions and pathways involved.

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In a long-term study, Chinese researchers find that conventional options may not be the only effective treatment for and prevention of gastric cancer