Carnosol activates Nrf2 leading to sestrin 2 induction in colon cells.

PMID: 

Integr Mol Med. 2018 Aug ;5(4). Epub 2018 Aug 15. PMID: 30972223

Abstract Title: 

Carnosol, a dietary diterpene from rosemary () activates Nrf2 leading to sestrin 2 induction in colon cells.

Abstract: 

Background: Rosemary is abundant with phytochemicals and has recently been approved as an antioxidant food preservative in the European Union. The safety of rosemary is well established, however, the benefits on gastrointestinal health are less known. Our overall hypothesis is that the phytochemicals in rosemary including carnosol have the potential to promote gastrointestinal health by activation of the antioxidant sestrin-2 when consumed in our diet.Methods: Colon cells HCT116 and SW480 were treated with carnosol and evaluated by MTT, immunofluorescence, ELISA, and Western blot analysis to understand the modulation of the PERK/Nrf2/Sestrin-2 pathway.Results: Carnosol was found to modulate PERK and increase the concentration of nuclear Nrf2. Furthermore, a downstream marker of Nrf2 expression, Sestrin-2 was shown to be upregulated.Conclusion: Based on these observations carnosol modulates the PERK and Nrf2 pathways along with increased expression of sestrin-2, a known stress inducible antioxidant.

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Rosmarinus officinalis L.: an update review of its phytochemistry and biological activity.

PMID: 

Future Sci OA. 2018 Apr ;4(4):FSO283. Epub 2018 Feb 1. PMID: 29682318

Abstract Title: 

L.: an update review of its phytochemistry and biological activity.

Abstract: 

The worldwide interest in the use of medicinal plants has been growing, and its beneficial effects being rediscovered for the development of new drugs. Based on their vast ethnopharmacological applications, which inspired current research in drug discovery, natural products can provide new and important leads against various pharmacological targets. This work pioneers an extensive and an updated literature review on the current state of research onL., elucidating which compounds and biological activities are the most relevant. Therefore, a search was made in the databases PubMed, ScienceDirect and Web of Science with the terms 'rosemary', '', 'rosmarinic acid' 'carnosol' and 'carnosic acid', which included 286 articles published since 1990 about rosemary's pharmacological activities and their isolated compounds. According to these references, there has been an increasing interest in the therapeutic properties of this plant, regarding carnosic acid, carnosol, rosmarinic acid and the essential oil. The present manuscript provides an updated review upon the most reported activities onand its active constituents.

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This study shows no risk of glioma associated with either short or medium term cell phone use. This is in agreement with some but not all studies.

PMID: 

BMJ. 2006 Apr 15 ;332(7546):883-7. Epub 2006 Jan 20. PMID: 16428250

Abstract Title: 

Mobile phone use and risk of glioma in adults: case-control study.

Abstract: 

OBJECTIVE: To investigate the risk of glioma in adults in relation to mobile phone use.DESIGN: Population based case-control study with collection of personal interview data.SETTING: Five areas of the United Kingdom.PARTICIPANTS: 966 people aged 18 to 69 years diagnosed with a glioma from 1 December 2000 to 29 February 2004 and 1716 controls randomly selected from general practitioner lists.MAIN OUTCOME MEASURES: Odds ratios for risk of glioma in relation to mobile phone use.RESULTS: The overall odds ratio for regular phone use was 0.94 (95% confidence interval 0.78 to 1.13). There was no relation for risk of glioma and time since first use, lifetime years of use, and cumulative number of calls and hours of use. A significant excess risk for reported phone use ipsilateral to the tumour (1.24, 1.02 to 1.52) was paralleled by a significant reduction in risk (0.75, 0.61 to 0.93) for contralateral use.CONCLUSIONS: Use of a mobile phone, either in the short or medium term, is not associated with an increased risk of glioma. This is consistent with most but not all published studies. The complementary positive and negative risks associated with ipsilateral and contralateral use of the phone in relation to the side of the tumour might be due to recall bias.

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Are Cannabidiol (CBD) Products Legal?

On a daily basis, we are asked, are CBD products really legal? And the answer is, yes!

For decades, growing hemp was prohibited until the 2014 Farm Bill made state-based hemp research programs legal. On December 12, the United States Congress voted to pass the Agriculture Improvement Act of 2018, more commonly referred to as the Farm Bill, with the signing of the Bill into law by the President on Thursday, December 20, 2018.

As well as including important policy extensions for certain areas in agricultural and nutritional policy for the next five years, the bill also confirms the legalization of hemp — the term given to cannabis containing less than 0.3% tetrahydrocannabinol (THC) — and provisions for its cultivation, transport, and sale.

Previous legislation, namely the 1937 Marihuana Tax Act and the 1970 Controlled Substances Act, failed to make any distinction between the cannabis and hemp plants – as a result, hemp was banned and classified as a Schedule 1 drug alongside cannabis in the same schedule as heroin, LSD, and ecstasy. With the passing of the Agricultural Improvement Act of 2018, that difference has now been officially recognized and the prohibition lifted.

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Cardamonin represses proliferation, invasion, and causes apoptosis in prostate cancer.

PMID: 

Apoptosis. 2017 01 ;22(1):158-168. PMID: 27900636

Abstract Title: 

Cardamonin represses proliferation, invasion, and causes apoptosis through the modulation of signal transducer and activator of transcription 3 pathway in prostate cancer.

Abstract: 

The pleiotropic transcription factor, signal transducer and activator of transcription 3 (STAT3) is often aberrantly activated in a wide variety of cancers and plays a pivotal role in tumor initiation, promotion and progression. Targeting deregulated STAT3 activation by small molecule inhibitors is generally considered as an important therapeutic strategy. Hence, in the present study, we evaluated the potential of cardamonin (CD), a 2',4'-dihydroxy-6'-methoxychalcone, to modulate STAT3 activation in prostate cancer (PC) cells and found that this chalcone can indeed exhibit significant anticancer effects through negatively regulating STAT3 activation by diverse molecular mechanism(s). CD suppressed STAT3 phosphorylation, nuclear translocation and DNA binding ability in PC cells. Computational modeling revealed that CD can bind directly to the Src Homology 2 domain of STAT3 and also effectively inhibit its dimerization. CD was also found to significantly reduce the migratory/invasive potential of PC cells through the downregulation of various oncogenic proteins. Overall, the data indicates that the potential application of CD as a STAT3 blocker can mitigate both the growth and survival of PC cells.

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Cardamonin attenuates hyperalgesia and allodynia in a mouse model of chronic constriction injury-induced neuropathic pain.

PMID: 

Eur J Pharmacol. 2017 Feb 5 ;796:32-38. Epub 2016 Dec 15. PMID: 27988285

Abstract Title: 

Cardamonin attenuates hyperalgesia and allodynia in a mouse model of chronic constriction injury-induced neuropathic pain: Possible involvement of the opioid system.

Abstract: 

Neuropathic pain arises from the injury of nervous system. The condition is extremely difficult to be treated due to the ineffectiveness and presence of various adverse effects of the currently available drugs. In the present study, we investigated the antiallodynic and antihyperlagesic properties of cardamonin, a naturally occurring chalcone in chronic constriction injury (CCI)-induced neuropathic pain mice model. Our findings showed that single and repeated dose of intra-peritoneal administration of cardamonin (3, 10, 30mg/kg) significantly inhibited (P

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Activation of Nrf2-driven antioxidant enzymes by cardamonin confers neuroprotection of PC12 cells against oxidative damage.

PMID: 

Food Funct. 2017 Mar 22 ;8(3):997-1007. PMID: 28271112

Abstract Title: 

Activation of Nrf2-driven antioxidant enzymes by cardamonin confers neuroprotection of PC12 cells against oxidative damage.

Abstract: 

Oxidative stress represents a disorder of the redox equilibrium between the production of free radicals and the capability of cells to eliminate them. As subversion of this redox balance is thought to initiate various diseases, living cells maintain a redox equilibrium diligently. More and more pieces of evidence show that oxidative stress has already become a common risk factor in the pathogenesis of neurodegenerative disorders. So, considerable importance has been given to the prevention of oxidative stress as a potential therapeutic strategy. It is well known that the Nrf2-ARE pathway represents one of the most important cellular endogenous defense mechanisms against oxidative stress. Activation of Nrf2 signaling induces the transcriptional regulation of multiple ARE-dependent antioxidant defense genes. Here, we showed that cardamonin (CD), a chalcone isolated from Alpinia katsumadai, attenuated cell death induced by hydrogen peroxide (HO) and 6-hydroxydopamine (6-OHDA) in PC12 cells. Pretreatment of PC12 cells with CD dose-dependently upregulated the expression of phase II antioxidant molecules governed by Nrf2. In contrast, CD failed to provide neuroprotection after silencing Nrf2 expression, indicating that this cytoprotection may be mediated by the activation of transcription factor Nrf2. Our results demonstrate that CD is a novel small molecule activator of Nrf2 in PC12 cells, and suggest that CD may be a potential candidate for the prevention of oxidative stress-mediated neurodegenerative disorders.

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Protective effect of cardamonin against acetic acid-induced ulcerative colitis in rats.

PMID: 

Pharmacol Rep. 2017 Apr ;69(2):268-275. Epub 2016 Nov 9. PMID: 28129600

Abstract Title: 

Protective effect of cardamonin against acetic acid-induced ulcerative colitis in rats.

Abstract: 

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease with significant morbidity. Cardamonin is a natural chalcone derivative with considerable anti-inflammatory activity. Herein, the potential protective effect of cardamonin against UC was tested in a rat model.METHODS: Rats were given 10 or 30mg/kg/day of cardamonin orally for 14days before induction of UC. On the 14th day of treatment, UC was induced by intrarectal instillation of 2ml 3% acetic acid. Twenty four h after acetic acid instillation, rats were sacrificed and colons were analyzed by macroscopic and histopathological examination. Colon lipid peroxidation was examined by biochemical evaluation of malondialdehyde (MDA). Myeloperoxidase (MPO), iNOS, NF-κB, TNFα levels were measured by ELISA. Moreover, caspase-3 and COX-2 were assessed by immunohistochemical analysis.RESULTS: Cardamonin at 10 and 30mg/kg decreased the disease activity index and macroscopic damage index scores, and significantly reduced histopathological deterioration. Additionally, cardamonin reduced levels of MPO, iNOS, NF-κB, TNFα and MDA (p

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Cardamonin could be a promising strategy in patients with hepatic Ischemia reperfusion injury.

PMID: 

Eur J Pharmacol. 2017 Nov 15 ;815:446-453. Epub 2017 Sep 28. PMID: 28966130

Abstract Title: 

Effect of cardamonin on hepatic ischemia reperfusion induced in rats: Role of nitric oxide.

Abstract: 

Ischemia reperfusion (I/R) injury is a cellular damage in a hypoxic organ following the restoration of oxygen delivery. It may occur during organ transplantation, trauma and hepatectomies. Nitric oxide (NO) effects during hepatic I/R are complicated. The iNOS-derived NO has a deleterious effect, whereas eNOS-derived NO has a protective effect in liver I/R. Cardamonin (CDN) is an anti-inflammatory molecule and a novel iNOS inhibitor, and Nω-Nitro-L-arginine (L-NNA) is a NOS inhibitor. L-Arginine is a precursor of NOS. This study was designed to investigate the possible protective effects of CDN on hepatic I/R and the role of NO. Wistar rats were randomly divided into 5 groups (Sham, I/R, CDN, L-NNA and L-arginine). Liver ischemia was induced for 45min then reperfusion was allowed for 1h. L-Arginine and CDN ameliorated the deleterious effects of I/R through reducing the oxidative stress and hepatocyte degeneration. Both molecules decreased the elevated inflammatory cytokines and increased the antiapoptotic marker, Bcl2. Both agents increased NO and eNOS expression and decreased iNOS expression. In conclusion, increased NO/eNOS and suppression of iNOS expression have protective effects on I/R injury. While inhibition of eNOS and reduction of NO have deleterious effects on I/R injury. For the first time, we demonstrated that cardamonin improved functional and structural abnormalities of the liver following I/R by improving oxidative stress and inflammation and increasing the availability of NO produced by eNOS. Treatment with cardamonin could be a promising strategy in patients with hepatic I/R injury in different clinical situations.

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