Tag Archives: curcumin

Curcumin nanoemulsion for treatment of intestinal inflammation

Most of my posts about research into curcumin (which is derived from turmeric) treatments has been based in India but this work according to a March 7, 2024 news item on phys.org comes from Brazil, Note: If you’re interested in more about turmeric/curcumin, I have a link to more information at the end of this posting,

A nanoemulsion containing particles of curcumin, which is known to have anti-inflammatory and antioxidant properties, has been found capable of modulating the gut microbiota of mice with intestinal inflammation in experiments conducted by researchers at the University of Western São Paulo (UNOESTE) and São Paulo State University (UNESP) in Brazil.

The image being used to illustrate an aspect of this research is a bit of a mystery. Is curcumin bright orange? And, it seems like a lot for a mouse,

Caption: The nanoemulsion enhanced the bioavailability of the curcumin and resulted in increased abundance of beneficial bacteria in the murine gut microbiota. Credit: UNOESTE

A March 6, 2024 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) press release (also on EurekAlert but published March 7, 2024) by Thais Szegö, which originated the news item, Note: Links have been removed,

Curcumin, a natural substance belonging to the group of bioactive compounds called curcuminoids, is a yellow polyphenolic pigment found in the turmeric plant (Curcuma longa). It has gained prominence in treatments to combat inflammatory intestinal disorders, but its bioavailability is low when it is administered orally. This problem is exacerbated in patients with Crohn’s disease, ulcerative colitis and other conditions associated with inflammation of the digestive tract and gut microbiota alterations. 

To enhance the efficacy of curcumin in such cases, the scientists developed an emulsion containing nanometric particles of the compound (invisible to the naked eye). “The research comprised two stages. The first entailed producing a nanoemulsion to deliver the curcumin. In the second, we evaluated its stability, morphology and physicochemical properties,” said Lizziane Kretli Winkelströter Eller, last author of the article and a professor at UNOESTE. 

Next, to test the action of the nanoemulsion in mice, the researchers induced intestinal inflammation using a drug called indomethacin and administered the nanoemulsion orally for 14 days. At the end of this period, they evaluated the intestinal inflammation by macroscopic, histopathological and metagenomic analysis.

The results showed that the nanoemulsion effectively improved the bioavailability of curcumin and modulated the gut microbiota of the mice after the damage was caused by the drug, increasing the presence there of beneficial bacteria. “The nanoemulsion didn’t lead to a significant improvement in the intestinal inflammation, but the relative abundance of Lactobacillus bacteria was about 25% higher in the mice treated with curcumin nanoemulsion than in the control group,” Eller said.

The authors of the study, the first to measure the effects of curcumin nanoemulsion in this way, stressed the importance of developing novel formulations that enhance the efficacy of curcumin in preventing and treating inflammatory bowel disease, since it has proved to be a valid alternative to existing treatments, which are expensive and have significant side effects. 

The group continues to conduct research on the potential of nanoformulations to deliver nutraceuticals (food elements of plant or animal origin with significant health benefits). “Specifically with regard to the curcumin nanoemulsion, we’re adjusting the formulation to increase the bioavailability of the active ingredient and will soon apply it in other protocols for the prevention and treatment of intestinal damage,” Eller said. 

About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

Here’s a link to and a citation for the paper,

Evaluation of curcumin nanoemulsion effect to prevent intestinal damage by Maria Vitória Minzoni de Souza Iacia, Maria Eduarda Ferraz Mendes, Karolinny Cristiny de Oliveira Vieira, Gilia Cristine Marques Ruiz, Carlos José Leopoldo Constantino, Cibely da Silva Martin, Aldo Eloizo Job, Gisele Alborghetti Nai, and Lizziane Kretli Winkelstroter Eller. International Journal of Pharmaceutics Volume 650, 25 January 2024, 123683 DOI: https://doi.org/10.1016/j.ijpharm.2023.123683

This paper is behind a paywall.

For the curious, Johns Hopkins Medical School has a posting by Mary-Eve Brown about turmeric, its benefits, and its use in Ayurvedic medicine.

Get your curcumin delivered by nanoparticles

Curcumin is a constituent of turmeric (used in cooking and as a remedy in Ayurvedic medicine). It’s been a while since I’ve stumbled across a curcumin story (scientists have been trying to find a way to exploit its therapeutic qualities for years). The latest news comes from Australia, which is a little unexpected as most of the ‘curcumin research stories’ previously on this blog have come from India.

A March 5, 2020 news item on ScienceDaily announces new research on curcumin therapeutic possibilities,

For years, curry lovers have sworn by the anti-inflammatory properties of turmeric, but its active compound, curcumin, has long frustrated scientists hoping to validate these claims with clinical studies.

The failure of the body to easily absorb curcumin has been a thorn in the side of medical researchers seeking scientific proof that curcumin can successfully treat cancer, heart disease, Alzheimer’s and many other chronic health conditions.

Now, researchers from the University of South Australia (UniSA), McMaster University in Canada and Texas A&M University have shown that curcumin can be delivered effectively into human cells via tiny nanoparticles.

Over three years ago on December 2, 2016, researchers from McMaster University made this video about Alzheimer’s and curcumin research available,

From the McMaster University, Centre for Health Economics & Policy Analysis, December 2, 2016 news webpage,

This video investigates the therapeutic potential of curcumin, a substance found in turmeric, to prevent Alzheimer’s disease. The information presented in this video has integrated research including in vitro studies that aimed to observe the influence of curcumin based interventions in the neuropathology of Alzheimer’s disease. From mechanisms for neurogenesis to the disintegration of beta amyloid plaques, this video highlights that there are many pathways by which curcumin can elicit its effects. However, there are currently not enough human trials to support the mouse-model studies for turmeric’s ability to prevent Alzheimer’s.

Back to the latest work, a March 5, 2020 UniSA press release (also on EurekAlert), which originated the news item, describes curcumin research that focuses on STI’s (sexually transmitted infections), also mentioned is earlier work on Alzheimer’s Disease,

Sanjay Garg, a professor of pharmaceutical science at UniSA, and his colleague Dr Ankit Parikh are part of an international team that has developed a nano formulation which changes curcumin’s behaviour to increase its oral bioavailability by 117 per cent.

The researchers have shown in animal experiments that nanoparticles containing curcumin not only prevents cognitive deterioration but also reverses the damage. This finding paves the way for clinical development trials for Alzheimer’s.

Co-author Professor Xin-Fu Zhou, a UniSA neuroscientist, says the new formulation offers a potential solution for Alzheimer’s disease.

“Curcumin is a compound that suppresses oxidative stress and inflammation, both key pathological factors for Alzheimer’s, and it also helps remove amyloid plaques, small fragments of protein that clump together in the brains of Alzheimer disease patients,” Prof Zhou says.

The same delivery method is now being tested to show that curcumin can also prevent the spread of genital herpes.

“To treat genital herpes (HSV-2) you need a form of curcumin that is better absorbed, which is why it needs to be encapsulated in a nano formulation,” Prof Garg says.

“Curcumin can stop the genital herpes virus, it helps in reducing the inflammation and makes it less susceptible to HIV and other STIs,” Prof Garg says.

Women are biologically more vulnerable to genital herpes as bacterial and viral infections in the female genital tract (FGT) impair the mucosal barrier. Curcumin, however, can minimize genital inflammation and control against HSV-2 infection, which would assist in the prevention of HIV infection in the FGT.

Here’s a link to and a citation for the latest paper,

Curcumin Can Decrease Tissue Inflammation and the Severity of HSV-2 Infection in the Female Reproductive Mucosa by Danielle Vitali, Puja Bagri, Jocelyn M. Wessels, Meenakshi Arora, Raghu Ganugula, Ankit Parikh, Talveer Mandur, Allison Felker, Sanjay Garg, M.N.V. Ravi Kumar, and Charu Kaushic. Int. J. Mol. Sci. 2020, 21(1), 337; DOI: https://doi.org/10.3390/ijms21010337 Published: 4 January 2020

This is an open access paper and is part of the journal’s Special Issue Curcumin in Health and Disease: New Knowledge)

For anyone interested in the earlier work on Alzheimer’s Disease, here are links to two papers that were published in 2018 by a team led by Sanjay Garg,

Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability by Ankit Parikh, Krishna Kathawala, Yunmei Song, Xin-Fu Zhou & Sanjay Garg. Drug Delivery and Translational Research volume 8, pages 1389–1405 (2018) DOI: https://doi.org/10.1007/s13346-018-0543-3 Issue Date: October 2018

Curcumin-loaded self-nanomicellizing solid dispersion system: part II: in vivo safety and efficacy assessment against behavior deficit in Alzheimer disease by Ankit Parikh, Krishna Kathawala, Jintao Li, Chi Chen, Zhengnan Shan, Xia Cao, Xin-Fu Zhou & Sanjay Garg. Drug Delivery and Translational Research volume 8, pages 1406–1420 (2018) DOI: https://doi.org/10.1007/s13346-018-0570-0 Issue Date: October 2018

Neither of these paper is open access but you can gain access by contacting sanjay.garg@unisa.edu.au

This looks like exciting work, bearing in mind the latest curcumin research on an STI was performed on female mice. As for the Alzheimer’s papers, that curcumin research was also performed on animals, presumably mice. As the press release noted, “This finding paves the way for clinical development trials for Alzheimer’s.” Oddly, there’s no mention of clinical trials for STI’s.

Bone regeneration with a mix of 21st century techniques and an age-old natural cure

Curry was how I was introduced to turmeric. My father who came from Mauritius loved curry and we had it at least once a week. Nobody mentioned healing properties, which I was to discover them only after I started this blog. Usually, turmeric is mentioned in cancer cures but not this time.

Turmeric Courtesy: Washington State University

From a May 2, 2018 Washington State University news release by Tina Hilding (also on EurekAlert but dated May 3, 2018),

A WSU research team is bringing together natural medical cures with modern biomedical devices in hopes of bringing about better health outcomes for people with bone diseases.

In this first-ever effort, the team improved bone-growing capabilities on 3D-printed, ceramic bone scaffolds by 30-45 percent when coated with curcumin, a compound found in the spice, turmeric. They have published their work in the journal, Materials Today Chemistry.

The work could be important for the millions of Americans who suffer from injuries or bone diseases like osteoporosis.

Human bone includes bone forming and resorbing cells that constantly remodel throughout our lives. As people age, the bone cell cycling process often doesn’t work as well. Bones become weaker and likely to fracture. Many of the medicines used for osteoporosis work by slowing down or stopping the destruction of old bone or by forming new bone. While they may increase bone density, they also create an imbalance in the natural bone remodeling cycle and may create poorer quality bone.

Turmeric has been used as medicine for centuries in Asian countries, and curcumin has been shown to have antioxidant, anti-inflammatory and bone-building capabilities. It can also prevent various forms of cancers. However, when taken orally as medicine, the compound can’t be absorbed well in the body. It is metabolized and eliminated too quickly.

Led by Susmita Bose, Herman and Brita Lindholm Endowed Chair Professor in the School of Mechanical and Materials Engineering, the researchers encased the curcumin within a water-loving polymer, a large molecule, so that it could be gradually released from their ceramic scaffolds. The curcumin increased the viability and proliferation of new bone cells and blood vessels in surrounding tissue as well as accelerated the healing process.

Bose hopes that the work will lead to medicines that naturally create healthier bone without affecting the bone remodeling cycle.

“In the end, it’s the bone quality that matters,” she said.

The researchers are continuing the studies, looking at the protein and cellular level to gain better understanding of exactly how the natural compound works. They are also working to improve the process’ efficiency and control. The challenge with the natural compounds, said Bose, is that they are often large organic molecules.

“You have to use the right vehicle for delivery,” she said. “We need to load and get it released in a controlled and sustained way. The chemistry of vehicle delivery is very important.”

In addition to curcumin, the researchers are studying other natural remedies, including compounds from aloe vera, saffron, Vitamin D, garlic, oregano and ginger. Bose is focused on compounds that might help with bone disorders, including those that encourage bone growth or that have anti-inflammatory, infection control, or anti-cancer properties.

Starting with her own health issues, Bose has had a longtime interest in bridging natural medicinal compounds with modern medicine. That interest increased after she had her children.

“As a mother and having a chemistry background, I realized I didn’t want my children to be exposed to so many chemicals for every illness,” Bose said. “I started looking at home remedies.”

To her students, she always emphasizes healthy living as the best way to guarantee the best health outcomes, including healthy eating, proper sleep, interesting hobbies, and exercise.

Courtesy Washington State University

Here’s a link to and a citation for the paper,

Effects of PCL, PEG and PLGA polymers on curcumin release from calcium phosphate matrix for in vitro and in vivo bone regeneration by Susmita Bose, Naboneeta Sarkar, Dishary Banerjee. Materials Today Chemistry Vol. 8 June 2018, pp. 110-130 [Published online May 2, 2018] https://doi.org/10.1016/j.mtchem.2018.03.005

This paper is behind a paywall.

Curcumin: a scientific literature review concludes health benefits may be overstated

Given the number of times I’ve featured ‘curcumin research’, it seems only right to include this latest work. A Jan. 11, 2017 American Chemical Society (ACS) news release (also on EurekAlert) describes the results of a review of the scientific literature on curcumin’s (a constituent of turmeric) medicinal effectiveness,

Curcumin, a compound in turmeric, continues to be hailed as a natural treatment for a wide range of health conditions, including cancer and Alzheimer’s disease. But a new review of the scientific literature on curcumin has found it’s probably not all it’s ground up to be. The report in ACS’ Journal of Medicinal Chemistry instead cites evidence that, contrary to numerous reports, the compound has limited — if any — therapeutic benefit.

Turmeric, a spice often added to curries and mustards because of its distinct flavor and color, has been used for centuries in traditional medicine. Since the early 1990’s, scientists have zeroed in on curcumin, which makes up about 3 to 5 percent of turmeric, as the potential constituent that might give turmeric its health-boosting properties. More than 120 clinical trials to test these claims have been or are in the process of being run by clinical investigators. To get to the root of curcumin’s essential medicinal chemistry, the research groups of Michael A. Walters and Guido F. Pauli teamed up to extract key findings from thousands of scientific articles on the topic.

The researchers’ review of the vast curcumin literature provides evidence that curcumin is unstable under physiological conditions and not readily absorbed by the body, properties that make it a poor therapeutic candidate. Additionally, they could find no evidence of a double-blind, placebo-controlled clinical trial on curcumin to support its status as a potential cure-all. But, the authors say, this doesn’t necessarily mean research on turmeric should halt [emphasis mine]. Turmeric extracts and preparations could have health benefits, although probably not for the number of conditions currently touted. The researchers suggest that future studies should take a more holistic approach to account for the spice’s chemically diverse constituents that may synergistically contribute to its potential benefits.

Here’s a link to and citation for the paper,

The Essential Medicinal Chemistry of Curcumin by Kathryn M. Nelson, Jayme L. Dahlin, Jonathan Bisson, James Graham, Guido F. Pauli, and Michael A. Walters. J. Med. Chem., Article ASAP DOI: 10.1021/acs.jmedchem.6b00975 Publication Date (Web): January 11, 2017

Copyright © 2017 American Chemical Society

This paper is open access.

Arbro Pharmaceuticals and its bioavailable curcumin

Curcumin (a constituent of the spice turmeric) is reputed to have health benefits and has been used in traditional medicine in Asia (notably India) for millenia. Recently scientists have been trying to render curcumin more effective which means increasing its bioavailability (my Nov. 7, 2014 posting features some of that research). According to an April 29, 2016 Arbro Pharmaceuticals press release, the goal of increased bioavailability has been reached and a product is now available commercially,

Arbro Pharmaceuticals has launched SNEC30, a patented highly bioavailable self-nanoemulsifying curcumin formulation in the dosage of 30mg.

Curcumin is the active ingredient of turmeric or haldi, which has been widely used in traditional medicine and home remedies in India for hundreds of years.

Clinical research conducted over the last 25 years has shown curcumin to be effective against various diseases like cancer, pain, inflammation, arthritis, ulcers, psoriasis, arteriosclerosis, diabetes and many more pro-inflammatory conditions.

Despite its effectiveness against so many medical conditions, scientists have come to believe that curcumin’s true potential has been limited by its poor bioavailability which is caused by the fact that it has poor solubility and extensive pre-systemic metabolism.

Arbro Pharmaceuticals partnered with Jamia Hamdard University to carry out research and develop a novel formulation, which can overcome curcumin’s poor bioavailability. The development project was jointly funded by Arbro and the Department of Science and Technology, Government of India under its DPRP (Drug and Pharmaceutical Research Programme) scheme.

SNEC30 is the outcome of this joint research and is based on a novel self-nanoemulsifying drug delivery systems (SNEDDS) for which patents have been filed and the US patent has been granted.

“There has been tremendous interest in the therapeutic potential of curcumin but its poor bioavailability was a limiting factor, our research group together with Arbro took the challenge and applied nanotechnology to overcome this limitation and achieve highest ever bioavailability for curcumin,” said Dr. Kanchan Kohli, Asst. Prof, Faculty of Pharmacy, Jamia Hamdard University, who is one of the main developers of the formulation.

Nanotechnology is the engineering of functional systems at the molecular scale (CRN – Centre for Responsible Nanotechnology). The name stems from the fact that the structures are in the nano-metre (10-9 mm) in range. In pharmaceutics, nano-formulations are used for targeted drug-delivery, particularly in cancer therapy. It also finds numerous other applications in medicine.

“Just 30mg of curcumin that is contained in one capsule of SNEC30 has shown higher blood levels than what can be achieved by consuming the curcumin content of 1kg of raw haldi or turmeric,” said Mr. Vijay Kumar Arora, Managing Director, Arbro Pharmaceuticals.

About Arbro Pharmaceuticals:

Arbro Pharmaceuticals is a 30-year-old research oriented company with its own research and development, testing and manufacturing facilities. Arbro has been manufacturing and exporting hundreds of formulations under its own brand name to more than 10 countries.

I am not endorsing this product but if you are interested the SNEC30 website is here. I believe Arbro Pharmaceuticals’ headquarters, the company which produces SNEC30, are located in India.

Researching a curcumin delivery system—a nutraceutical story

A Nov. 6, 2014 news item on ScienceDaily features research on delivering curcumin’s (a constituent of turmeric) health benefits more efficiently (there is a twist; for the impatient, you may want to scroll down to where I provide an excerpt from the university’s news release) from Ohio State University (US),

The health benefits of over-the-counter curcumin supplements might not get past your gut, but new research shows that a modified formulation of the spice releases its anti-inflammatory goodness throughout the body.

Curcumin is a naturally occurring compound found in the spice turmeric that has been used for centuries as an Ayurvedic medicine treatment for such ailments as allergies, diabetes and ulcers.

Anecdotal and scientific evidence suggests curcumin promotes health because it lowers inflammation, but it is not absorbed well by the body. Most curcumin in food or supplements stays in the gastrointestinal tract, and any portion that’s absorbed is metabolized quickly.

A Nov. 6, 2014 Ohio State University news release by Emily Caldwell (also on EurekAlert), which originated the news item, explains the interest in curcumin in more detail and describes the research in more detail,

Many research groups are testing the compound’s effects on disorders ranging from colon cancer to osteoarthritis. Others, like these Ohio State University scientists, are investigating whether enabling widespread availability of curcumin’s biological effects to the entire body could make it useful both therapeutically and as a daily supplement to combat disease.

“There’s a reason why this compound has been used for hundreds of years in Eastern medicine. And this study suggests that we have identified a better and more effective way to deliver curcumin and know what diseases to use it for so that we can take advantage of its anti-inflammatory power,” said Nicholas Young, a postdoctoral researcher in rheumatology and immunology at Ohio State and lead author of the study.

Curcumin powder was mixed with castor oil and polyethylene glycol in a process called nano-emulsion (think vinaigrette salad dressing), creating fluid teeming with microvesicles that contain curcumin. This process allows the compound to dissolve and be more easily absorbed by the gut to enter the bloodstream and tissues.

Feeding mice this curcumin-based drug shut down an acute inflammatory reaction by blocking activation of a key protein that triggers the immune response. The researchers were also the first to show that curcumin stops recruitment of specific immune cells that, when overactive, are linked to such problems as heart disease and obesity.

Young and his colleagues, including co-senior authors Lai-Chu Wu and Wael Jarjour of the Division of Rheumatology and Immunology at Ohio State’s Wexner Medical Center, now want to know if curcumin in this form can counter the chronic inflammation that is linked to sickness and age-related frailty. They have started with animal studies testing nano-emulsified curcumin’s ability to prevent or control inflammation in a lupus model.

“We envision that this nutraceutical could be used one day both as a daily supplement to help prevent certain diseases and as a therapeutic drug to help combat the bad inflammation observed in many diseases,” Young said. “The distinction will then be in the amount given – perhaps a low dose for daily prevention and higher doses for disease suppression.”

The term nutraceutical refers to foods or nutrients that provide medical or health benefits.

This news release notes the latest research is built on previous work,

The curcumin delivery system was created in Ohio State’s College of Pharmacy, and these researchers previously showed that concentrations of the emulsified curcumin in blood were more than 10 times higher than of curcumin powder suspended in water.

A more precise description of the current research is then provided (from the news release),

… From there, the researchers launched experiments in mice and cell cultures, generating artificial inflammation and comparing the effects of the nano-emulsified curcumin with the effects of curcumin powder in water or no treatment at all. [emphasis mine]

The researchers injected mice with lipopolysaccharide, a bacteria cell wall extract that stimulates an immune reaction in animals. Curcumin can target many molecules, but the research team zeroed in on NF-kB, a protein that is known to play an important role in the immune response.

In a specialized imaging machine, mice receiving plain curcumin lit up with bioluminescent signals indicating that NF-kB was actively triggering an immune response, while mice receiving nano-emulsified curcumin showed minimal signs – a 22-fold reduction – that the protein had been activated at all.

Knowing that curcumin delivered in this way could shut down NF-kB activation throughout the animals’ bodies, researchers looked for further details about the compound’s effects on inflammation. They found that nano-emulsified curcumin halted the recruitment of immune cells called macrophages that “eat” invading pathogens but also contribute to inflammation by secreting pro-inflammatory chemicals. And in cells isolated from human blood samples, macrophages were stopped in their tracks.

“This macrophage-specific effect of curcumin had not been described before,” Young said. “Because of that finding, we propose nano-emulsified curcumin has the best potential against macrophage-associated inflammation.”

Inflammation triggered by overactive macrophages has been linked to cardiovascular disease, disorders that accompany obesity, Crohn’s disease, rheumatoid arthritis, inflammatory bowel disease, diabetes and lupus-related nephritis.

Here’s a link to and a citation for the paper,

Oral Administration of Nano-Emulsion Curcumin in Mice Suppresses Inflammatory-Induced NFκB Signaling and Macrophage Migration by Nicholas A. Young, Michael S. Bruss, Mark Gardner, William L. Willis, Xiaokui Mo, Giancarlo R. Valiente, Yu Cao, Zhongfa Liu, Wael N. Jarjour, and Lai-Chu Wu. PLOS ONE Published: November 04, 2014 DOI: 10.1371/journal.pone.0111559

This paper is open accesss.

I have an Oct. 1, 2014 posting which features research on curcumin for healing wounds and on tumerone for stimulating the formation of stem cells in the brain.

Wonders of curcumin: wound healing; wonders of aromatic-turmerone: stem cells

Both curcumin and turmerone are constituents of turmeric which has been long lauded for its healing properties. Michael Berger has written a Nanowerk Spotlight article featuring curcumin and some recent work on burn wound healing. Meanwhile, a ScienceDaily news item details information about a team of researchers focused on tumerone as a means for regenerating brain stem cells.

Curcumin and burn wounds

In a Sept. 22, 2014 Nanowerk Spotlight article Michael Berger sums up the curcumin research effort (referencing some of this previous articles on the topic) in light of a new research paper about burn wound healing (Note: Links have been removed),

Despite significant progress in medical treatments of severe burn wounds, infection and subsequent sepsis persist as frequent causes of morbidity and mortality for burn victims. This is due not only to the extensive compromise of the protective barrier against microbial invasion, but also as a result of growing pathogen resistance to therapeutic options.

… Dr Adam Friedman, Assistant Professor of Dermatology and Director of Dermatologic research at the Montefiore-Albert Einstein College of Medicine, tells Nanowerk. “For me, this gap fuels innovation, serving as the inspiration for my research with broad-spectrum, multi-mechanistic antimicrobial nanomaterials.”

In new work, Friedman and a team of researchers from Albert Einstein College of Medicine and Oregon State University have explored the use of curcumin nanoparticles for the treatment of infected burn wounds, an application that resulted in reduced bacterial load and enhancing wound healing.

It certainly seems promising as per the article abstract,

Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent by Aimee E. Krausz, Brandon L. Adler, Vitor Cabral, Mahantesh Navati, Jessica Doerner, Rabab Charafeddine, Dinesh Chandra, Hongying Liang, Leslie Gunther, Alicea Clendaniel, Stacey Harper, Joel M. Friedman, Joshua D. Nosanchuk, & Adam J. Friedman. Nanomedicine: Nanotechnology, Biology and Medicine (article in press) published online 19 September 2014.http://www.nanomedjournal.com/article/S1549-9634%2814%2900527-9/abstract Uncorrected Proof

Burn wounds are often complicated by bacterial infection, contributing to morbidity and mortality. Agents commonly used to treat burn wound infection are limited by toxicity, incomplete microbial coverage, inadequate penetration, and rising resistance. Curcumin is a naturally derived substance with innate antimicrobial and wound healing properties. Acting by multiple mechanisms, curcumin is less likely than current antibiotics to select for resistant bacteria.

Curcumin’s poor aqueous solubility and rapid degradation profile hinder usage; nanoparticle encapsulation overcomes this pitfall and enables extended topical delivery of curcumin.

In this study, we synthesized and characterized curcumin nanoparticles (curc-np), which inhibited in vitro growth of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in dose-dependent fashion, and inhibited MRSA growth and enhanced wound healing in an in vivo murine wound model. Curc-np may represent a novel topical antimicrobial and wound healing adjuvant for infected burn wounds and other cutaneous injuries.

Two things: This paper is behind a paywall and note the use of the term ‘in vivo’ which means they have tested on animals such as rats and mice for example, but not humans. Nonetheless, it seems a promising avenue for further exploration.

Interestingly, there was an attempt in 1995 to patent turmeric for use in wound healing as per my Dec. 26, 2011 posting which featured then current research on turmeric,

There has already been one court case regarding a curcumin patent,

Recently, turmeric came into the global limelight when the controversial patent “Use of Turmeric in Wound Healing” was awarded, in 1995, to the University of Mississippi Medical Center, USA. Indian Council of Scientific and Industrial Research (CSIR) aggressively contested this award of the patent. It was argued by them that turmeric has been an integral part of the traditional Indian medicinal system over several centuries, and therefore, is deemed to be ‘prior art’, hence is in the public domain. Subsequently, after protracted technical/legal battle USPTO decreed that turmeric is an Indian discovery and revoked the patent.

One last bit about curcumin, my April 22, 2014 posting featured work in Iran using curcumin for cancer-healing.

Tumerone

This excerpt from a Sept. 25, 2014, news item in ScienceDaily represents the first time that tumerone has been mentioned here,

A bioactive compound found in turmeric promotes stem cell proliferation and differentiation in the brain, reveals new research published today in the open access journal Stem Cell Research & Therapy. The findings suggest aromatic turmerone could be a future drug candidate for treating neurological disorders, such as stroke and Alzheimer’s disease.

A Sept. 25, 2014 news release on EurekAlert provides more information,

The study looked at the effects of aromatic (ar-) turmerone on endogenous neutral stem cells (NSC), which are stem cells found within adult brains. NSC differentiate into neurons, and play an important role in self-repair and recovery of brain function in neurodegenerative diseases. Previous studies of ar-turmerone have shown that the compound can block activation of microglia cells. When activated, these cells cause neuroinflammation, which is associated with different neurological disorders. However, ar-turmerone’s impact on the brain’s capacity to self-repair was unknown.

Researchers from the Institute of Neuroscience and Medicine in Jülich, Germany, studied the effects of ar-turmerone on NSC proliferation and differentiation both in vitro and in vivo. Rat fetal NSC were cultured and grown in six different concentrations of ar-turmerone over a 72 hour period. At certain concentrations, ar-turmerone was shown to increase NSC proliferation by up to 80%, without having any impact on cell death. The cell differentiation process also accelerated in ar-turmerone-treated cells compared to untreated control cells.

To test the effects of ar-turmerone on NSC in vivo, the researchers injected adult rats with ar-turmerone. Using PET imaging and a tracer to detect proliferating cells, they found that the subventricular zone (SVZ) was wider, and the hippocampus expanded, in the brains of rats injected with ar-turmerone than in control animals. The SVZ and hippocampus are the two sites in adult mammalian brains where neurogenesis, the growth of neurons, is known to occur.

Lead author of the study, Adele Rueger, said: “While several substances have been described to promote stem cell proliferation in the brain, fewer drugs additionally promote the differentiation of stem cells into neurons, which constitutes a major goal in regenerative medicine. Our findings on aromatic turmerone take us one step closer to achieving this goal.”

Ar-turmerone is the lesser-studied of two major bioactive compounds found in turmeric. The other compound is curcumin, which is well known for its anti-inflammatory and neuroprotective properties

Here’s a link to and a citation for the paper,

Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo by Joerg Hucklenbroich, Rebecca Klein, Bernd Neumaier, Rudolf Graf, Gereon Rudolf Fink, Michael Schroeter, and Maria Adele Rueger. Stem Cell Research & Therapy 2014, 5:100  doi:10.1186/scrt500

This is an open access paper.

Iran’s work on turmeric (curcumin) as an anti-cancer drug

It’s been a while since I’ve mentioned either Iran or curcumin (a constituent of turmeric) but an April 15, 2014 news item on Nanowerk has given me an opportunity to do both,

Nanotechnology researchers from Tarbiat Modarres University [Iran] produced a new drug capable of detecting and removing cancer cells using turmeric …

The compound is made of curcumin found in the extract of turmeric, and has desirable physical and chemical stability and prevents the proliferation of cancer cells.

An April 16, 2014 Iran Nanotechnology Initiative Council (INIC) news release, which despite its date appears to have originated the news item, fills in details about the research,

In this drug, curcumin with high efficiency (approximately 87%) was loaded in the polymeric nanocarrier, and it created a spherical structure with the size of 140 nm. The drug has high physical and chemical stability. The drug was used successfully in laboratory conditions in the treatment of a type of aggressive tumor in the central nervous system, called glioblastoma (GBM).

The interesting point is that the fatal effect of nanocurcumin on mature stem cells derived from marrow and natural cells of skin fibroblast is observed at a concentration higher than a concentration that is effective on cancer cells. In other words, no fatal effect on natural cells is observed at concentrations that are fatal to cancer cells. It shows that curcumin prefers to enter cancer cells.

The size range of the nanocarrier used in this research is 15-100 nm. Physical and chemical stability, non-toxicity, and biodegradability are among the main characteristics of the nanocarriers. Based on the results, the nanocarrier used in this research has no toxic effect on cells. In other words, all the death in the cells is caused by curcumin, and dendrosome only results in bioavailability and transference of the drug into the cells.

“The drug has the potential to affect a number of message delivery paths in the cells, one of which is cell proliferation path. Therefore, the drug prefers to enter cancer cells rather than various types of natural cells,” the researchers said.

Here’s a link to and a citation for the paper,

Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells by Maryam Tahmasebi Mirgani, Benedetta Isacchi, Majid Sadeghizadeh, Fabio Marra, Anna Rita Bilia, Seyed Javad Mowla, Farhood Najafi, & Esmael Babaei. International Journal of Nanomedicine, vol. 9, issue 1, January 2014, pp. 403-417.DOI: http://dx.doi.org/10.2147/IJN.S48136

This is an open access paper.

I last wrote about turmeric or more specifically curcumin in a December 25, 2011 posting about research at UCLA (University of California at Los Angeles).

At the nanoscale, grapefruit swings from being medication danger to medication enhancer

It’s known that grapefruit, despite its health benefits, can inhibit (or even a pose danger) to a medication’s effectiveness. Most of us have been warned at one time or another to avoid grapefruit juice when downing a pill. So, the news from the University of Louisville (Kentucky; UofL) about grapefruit as part of a drug delivery system seems a little counter-intuitive (from the May 22, 2013 news item on Azonano),

Grapefruits have long been known for their health benefits, and the subtropical fruit may revolutionize how medical therapies like anti-cancer drugs are delivered to specific tumor cells.

University of Louisville researchers have uncovered how to create nanoparticles using natural lipids derived from grapefruit, and have discovered how to use them as drug delivery vehicles. UofL scientists Huang-Ge Zhang, D.V.M., Ph.D., Qilong Wang, Ph.D., and their team today (May 21, 2013), published their findings in Nature Communications.

The May 21, 2013 University of Louisville news release by Julie Heflin, which originated the news item, describes how the nanoparticles are derived and their advantages,

“These nanoparticles, which we’ve named grapefruit-derived nanovectors (GNVs), are derived from an edible plant, and we believe they are less toxic for patients, result in less biohazardous waste for the environment and are much cheaper to produce at large scale than nanoparticles made from synthetic materials,” said Zhang, who holds the Founders Chair in Cancer Research at the Brown Cancer Center.

The researchers demonstrated that GNVs can transport various therapeutic agents, including anti-cancer drugs, DNA/RNA and proteins such as antibodies. Treatment of animals with GNVs seemed to cause less adverse effects than treatment with drugs encapsulated in synthetic lipids.

“Our GNVs can be modified to target specific cells — we can use them like missiles to carry a variety of therapeutic agents for the purpose of destroying diseased cells,” he said. “Furthermore, we can do this at an affordable price.”

The therapeutic potential of grapefruit derived nanoparticles was further validated through a Phase 1 clinical trial for treatment of colon cancer patients. So far, researchers have observed no toxicity in the patients who orally took the anti-inflammatory agent curcumin encapsulated in grapefruit nanoparticles.

The UofL scientists also plan to test whether this technology can be applied in the treatment of inflammation related autoimmune diseases like rheumatoid arthritis.

Here’s a link to and a citation for the researchers’ paper,

Delivery of therapeutic agents by nanoparticles made of grapefruit-derived lipids by Qilong Wang, Xiaoying Zhuang, Jingyao Mu, Zhong-Bin Deng, Hong Jiang, Xiaoyu Xiang, Baomei Wang, Jun Yan, Donald Miller, & Huang-Ge Zhang. Nature Communications 4, 1867 doi:10.1038/ncomms2886 Published 21 May 2013

This paper is behind a paywall.

As for the dangers of grapefruit-medication interactions, ABC (American Broadcasting Corporation) has a Nov. 26, 2012 news item featuring then new research suggesting that even more medications are affected by grapefruit/grapefruit juice than had previously been believed,

It has long been known that grapefruit juice can pose dangerous — and even deadly — risks when taken along with certain medications. Now, experts warn the list of medications that can result in these interactions is longer than many may have believed.

In a new report released Monday in the Canadian Medical Association Journal [CMAJ], researchers at the University of Western Ontario said that while 17 drugs were identified in 2008 as having the potential to cause serious problems when taken with grapefruit, this number has now grown to 43.

So how does a common breakfast fruit cause these problems? Grapefruits contain chemicals called furanocoumarins that interfere with how your body breaks down drugs before they enter the bloodstream. By preventing this normal breakdown of a drug, these chemicals in grapefruit can effectively cause a drug overdose and more severe side-effects.

Among the side effects sometimes seen with grapefruit-induced overdoses are heart rhythm problems, kidney failure, muscle breakdown, difficulty with breathing and blood clots. …

ABC provides a list of drugs that are affected by grapefruit here.

For interested parties, here’s a link to and a citation for the research on grapefruit-medication interactions,

Grapefruit–medication interactions: Forbidden fruit or avoidable consequences? by David G. Bailey, George Dresser, and J. Malcolm O. Arnold. CMAJ March 5, 2013 185:309-316; published ahead of print November 26, 2012,

This paper is behind a paywall.

I have a couple of final comments. (1) It would seem that the grapefruit’s characteristics at the macroscale are not echoed at the nanoscale. (2) Interestingly, the grapefruit nanoparticles (grapefruit nanovectors [GNVs]) are being used to encapsulate curcumin (a constituent of turmeric). I wrote about turmeric and its healing properties in a Dec. 26, 2011 posting, which features a number of links to research in this area.

Turmeric, healing, and nanotechnology

Turmeric gives its distinctive yellow colour to the type of curry we always ate at home. All these years later, it’s a bit of a surprise to learn that turmeric has healing properties. From the Sept. 13, 2011 news item on MedicalXpress.com,

Curcumin, the main component in the spice turmeric, suppresses a cell signaling pathway that drives the growth of head and neck cancer, according to a pilot study using human saliva by researchers at UCLA’s Jonsson Comprehensive Cancer Center.

“This study shows that curcumin can work in the mouths of patients with head and neck malignancies and reduce activities that promote cancer growth,” Wang [Dr. Marilene Wang, senior author and professor of head and neck surgery] said. “And it not only affected the cancer by inhibiting a critical cell signaling pathway, it also affected the saliva itself by reducing pro-inflammatory cytokines within the saliva.”

Unfortunately, the amounts used in cooking are not sufficient for a cancer inhibiting effect,

To be effective in fighting cancer, the curcumin must be used in supplement form. Although turmeric is used in cooking, the amount of curcumin needed to produce a clinical response is much larger. Expecting a positive effect through eating foods spiced with turmeric is not realistic, Wang said.

There is a bit of a downside to the type of supplement they used in this study,

The curcumin was well tolerated by the patients and resulted in no toxic effects. The biggest problem was their mouths and teeth turned bright yellow.

As you might expect, the next study will be for a longer period,

The next step for Wang and her team is to treat patients with curcumin for longer periods of time to see if the inhibitory effects can be increased. They plan to treat cancer patients scheduled for surgery for a few weeks prior to their procedure. They’ll take a biopsy before the curcumin is started and then at the time of surgery and analyze the tissue to look for differences.

“There’s potential here for the development of curcumin as an adjuvant treatment for cancer,” Wang said. “It’s not toxic, well tolerated, cheap and easily obtained in any health food store. While this is a promising pilot study, it’s important to expand our work to more patients to confirm our findings.”

There have been two feature articles on Nanowerk about curcumin, its healing properties, which extend beyond treating head and neck cancer, and patents during fall 2011. From the Sept. 8, 2011 article, Nanotechnology-enhanced curcumin: Symbiosis of ancient wisdom of the East with modern medical science [Note: I have removed citation notes],

Turmeric (Curcuma longa L.) is the shining star among the cornucopia of traditional medicinal plants. It has a long history of usage in traditional medicine in India and China. Ancient Indians have known the medicinal properties of turmeric, thus curcumin, for several millennia.

The cultivation of turmeric plants began in Harappan civilization in 3000 BC and Susruta Samhita, dating back to 250 BC, highly recommends use of an ointment based on turmeric for relieving food poisoning effect. Turmeric was introduced to China from India by 700 A.D. and has been said to be long used as a medicinal herb. It has been used in Ayurvedic medicines internally as a stomach tonic and blood purifier, and topically in the prevention and treatment of skin diseases.

In the scientific literature there is a large body of evidence showing that curcuminoids exhibit a broad spectrum of biological and pharmacological activities including anti-oxidant, anti-inflammatory, anti-bacterial, anti-fungal, anti-parasitic, anti-mutagen, anti-cancer and detox properties. Curcumin’s unique ability to work through so many different pathways with its extraordinary antioxidant and anti-inflammatory attributes can have a positive influence in combating almost every known disease.

Extensive studies carried out by researchers around the globe have clearly demonstrated curcumin’s great potential as a thercurcuminapeutic agent, and have paved the way towards conducting clinical trials for a variety of diseases including cancer, cardiovascular, neurological and gastrointestinal disorders, multiple sclerosis, diabetes type II, skin diseases, cystic fibrosis, cataract etc.  [Note: There is also an extensive discussion of cancer treatment included in this article.]

Here are the active components (as understood by scientists currently),

The bio-active polyphenol component of turmeric is curcumin, also known as diferuloylmethane (C21H20O6), with an ability to prevent and cure diseases. Turmeric contains about 2-5% curcumin alone. Commercial curcumin contains three main types of curcuminoids, i.e., curcumin (diferuloylmethane or”Curcumin I” about 77%), demethoxy curcumin (“Curcumin II” ∼17%) and bis demethoxy curcumin (“Curcumin III” ∼3%)). Curcumin (diferuloylmethane renders its bright yellow color to turmeric. In addition to natural curcumin, several analogues of curcumin have been synthesized and studied. These include tetrahydrocurcumin (antioxidative), 4-hydroxy-3-methoxybenzoic acid methyl ester (HMBME), aromatic enone and dienone analogues, metal chelates of synthetic curcuminoids etc.

There has already been one court case regarding a curcumin patent,

Recently, turmeric came into the global limelight when the controversial patent “Use of Turmeric in Wound Healing” was awarded, in 1995, to the University of Mississippi Medical Center, USA. Indian Council of Scientific and Industrial Research (CSIR) aggressively contested this award of the patent. It was argued by them that turmeric has been an integral part of the traditional Indian medicinal system over several centuries, and therefore, is deemed to be ‘prior art’, hence is in the public domain. Subsequently, after protracted technical/legal battle USPTO decreed that turmeric is an Indian discovery and revoked the patent.

I wonder if this will set a precedent for other herbs and plants that are associated with specific cultures or indigenous groups as part of their healing tradition. Much of our modern pharamcopoeia is derived from traditional healing plants and the people who shared that knowledge have not shared in the benefits that large pharmaceutical companies have reaped.

Back to the curcumin and the issue of low bioavailability (in Wang’s study mentioned earlier, patients were given 2 tablets totaling 1000 miligrams of curcumin and it seems that was done once),

In practice, only very low or undetectable levels of curcumin can be achieved in blood by oral administration of curcumin. The low bioavailability of curcumin has been attributed to its very low aqueous solubility, tendency to degrade in the gastroinenstinal tract in the physiological environment, high rate of metabolism, and rapid systemic elimination. The low bioavailability of curcumin has so far limited its medical use. It has been suggested that a person is required to consume large doses (about 12-20g/day) of curcumin in order to achieve its therapeutic effects on the human body. That means one has to swallow 24 to 40 curcumin capsules of 500mg each. These doses are considered to be too high, and therefore, not feasible to be incorporated in clinical trials due to unbearable after-taste to the palate, possibility of giving rise to nauseatic feeling and perceived toxicity issues.

Therefore, to achieve the maximum response of this potentially useful chemopreventive agent, a number of approaches such as the use of adjuvants like piperine, synthetic analogues, chelating of curcumin with metals, combination with other dietary agents etc. have been investigated. Nanotechnology-based novel strategies are being aggressively explored worldwide to enhance curcumin’s bioavailability and reduce perceived toxicity as they offer several other additional benefits such as improved cellular uptake, enhanced dissolution rates, excellent blood stability, controlled release functions, multifunctional design, enhancement in its pharmacological activities (e.g. antioxidant and antihepatoma activities) etc.

This article and the Dec. 22, 2011 article, Nanotechnology-enhanced curcumin – literature and patent analysis, on Nanowerk were both written by Dr. Yashwant Mahajan (by himself for the Sept. 8  article and with Ratnesh Kumar Gaur for the Dec. 22 article), Centre for Knowledge Management of Nanoscience and Technology (CKMNT). There is more detail about the nanotechnology-based strategies to increase bioavailability in the Dec. 22, 1011 article,

These approaches include solid-lipid nanoparticles, nanosuspension, nanoemulsion, cyclodextrin curcumin self assembly, hydrogel nanoparticles, curcumin-phospholipid complex and curcumin incorporated within polymer nanoparticles. The figure below shows these various nano-based approaches for drug delivery of curcumin in the form of a pie chart and this survey is based on 124 relevant patents for the period from 2001 to 2010. As depicted in this pie chart [in the article on Nanowerk] polymer nanoparticles play a dominant role (34%) followed by curcumin nanoemulsion (20%), nanosuspension (13%), phospholipids complex (12%), cyclodextrin curcumin self-assembly, hydrogel NPs and SLNs in decreasing order. The polymer nanoparticles-incorporated drug delivery systems are further subdivided into various classes of polymers such as generic polymers, liposomal, PEG, micelle, PLGA, and as can be seen, generic polymers, liposomal, PEG and micelle play a dominant role in decreasing order.

Curcumin is still being patented but it seems the focus on delivering curcumin more efficiently for therapeutic use,

The analysis reveals that Laila Pharmaceuticals Private Ltd., Chennai, India is the world leader with 8 patent applications to their credit and their main focus is on nanoemulsification of curcumin and its derivatives. Second in the ranking are Johns Hopkins University, USA, and University of North Texas, USA with 7 patent applications each to their credit and their inventions are directed towards use of polymer nanoparticle encapsulated curcumin and curcumin loaded with PLGA-nanoparticles, respectively. The analysis has also revealed that R&D institutes, universities and only a few small bio and pharma companies such as Laila Pharmaceuticals, Magforce Nanotechnologies, Bioderm Research, Nano Cutting Edge Technologies etc. are involved in the patenting activity.

I did check out the Centre for Knowledge Management of Nanoscience and Technology (CKMNT) where Dr. Mahajan works and which was launched in 2009. From the About Us page,

CKMNT was launched on 1st April 2009 at Hyderabad by the International Advanced Research Centre for Powder Metallurgy and New Materials (ARCI) as one of its project centres. The centre has been set up to foster the exchange and dissemination of advanced technological knowledge and expertise to meet the needs of the nanoresearchers, industry, policy makers, financial institutions and venture capitalists. CKMNT has been partially funded by the Department of Science and Technology (DST), Govt. of India in a project mode and would help in fulfilling the objectives of the Nano Mission of DST.

The Centre’s team is made up of metallurgy and chemical engineering experts, none of whom seem to have worked in medicine or health care, which makes this interest in turmeric a little surprising.