Seeking HIV Treatment Clues in the Neem Tree

Preliminary data hint at how extracts from the tree, abundant in tropical and subtropical areas, may stop the virus from multiplying 

Tall, with dark-green pointy leaves, the neem tree of India is known as the “village pharmacy.” As a child growing up in metropolitan New Delhi, Sonia Arora recalls on visits to rural areas seeing villagers using neem bark to clean their teeth. Arora’s childhood memories have developed into a scientific fascination with natural products and their power to cure illnesses. Now an assistant professor at Kean University in New Jersey, Arora is delving into understanding the curative properties of the neem tree in fighting the virus that causes AIDS. Sonia Arora presented her data at a poster session Sunday, April 22, at the Experimental Biology 2012 meeting in San Diego. Her preliminary results seem to indicate that there are compounds in neem extracts that target a protein essential for HIV to replicate. If further studies support her findings, Arora’s work may give clinicians and drug developers a new HIV-AIDS therapy to pursue. Extracts from neem leaves, bark and flowers are used throughout the Indian subcontinent to fight against pathogenic bacteria and fungi. “The farther you go into the villages of India, the more uses of neem you see,” says Arora. Tree branches are used instead of toothpaste and toothbrushes to keep teeth and gums healthy, and neem extracts are used to control the spread of malaria. Practitioners of Ayurvedic medicine, a form of traditional Indian alternative medicine, even prescribe neem extracts, in combination with other herbs, to treat cardiovascular diseases and control diabetes. The neem tree, whose species name is Azadirachta indica and which belongs to the mahogany family, also grows in east Africa. Arora’s scientific training gave her expertise in the cellular biology of cancer, pharmacology, bioinformatics and structural biology. When she established her laboratory with a new research direction at Kean University in 2008, Arora decided to combine her knowledge with her long-time fascination with natural products. The neem tree beckoned. Arora dived into the scientific literature to see what was known about neem extracts. During the course of her reading, Arora stumbled across two reports that showed that when HIV-AIDS patients in Nigeria and India were given neem extracts, the amount of HIV particles in their blood dropped. Intrigued, Arora decided to see if she could figure out what was in the neem extract that seemed to fight off the virus. She turned to bioinformatics and structural biology to see what insights could be gleaned from making computer models of HIV proteins with compounds known to be in neem extracts. From the literature, she and her students found 20 compounds present in various types of neem extracts. When they modeled these compounds against the proteins critical for the HIV life-cycle, Arora and her team discovered that most of the neem compounds attacked the HIV protease, a protein essential for making new copies of the virus. Arora’s group is now working on test-tube experiments to see if the computer models hold up with actual samples. If her work bears out, Arora is hopeful that the neem tree will give a cheaper and more accessible way to fight the HIV-AIDS epidemic in developing countries, where current therapies are priced at levels out of reach of many people. “And, of course,” she notes, “there is the potential of discovering new drugs based on the molecules present in neem.”

CoQ10 Levels Reduced In Septic Shock

The first report on the levels of CoQ10 in human subjects with septic shock was published online on August 9, 2011 in the journal Critical Care. Sepsis is an inflammatory state resulting from the spread of infectious agents in the bloodstream. Sepsis and septic shock are a major cause of illness and mortality in the USA, with over 215,000 deaths occurring each year. The finding in this study that CoQ10 is low in sepsis opens the possibility for potential therapeutic intervention as CoQ10 can be administered exogenously. 

 

Michael W Donnino, Michael N Cocchi, Justin D Salciccioli, Daniel Kim, Ali Naini, Catherine Buettner and Praveen Akuthota
Coenzyme Q10 levels are low and are associated with the inflammatory cascade in septic shock
Critical Care 2011; 15 (4): R189. [Epub ahead of print]


ABSTRACT

Introduction:
Mitochondrial dysfunction is associated with increased mortality in septic shock. Coenzyme Q10 (CoQ10) is a key cofactor in the mitochondrial respiratory chain but whether CoQ10 is depleted in septic shock remains unknown. Moreover, statin therapy may decrease CoQ10 levels but whether this occurs acutely remains unknown. We measured CoQ10 levels in septic shock patients enrolled in a randomized trial of simvastatin versus placebo.

Methods:
Post-hoc analysis of a prospective randomized trial of simvastatin versus placebo in patients with septic shock (ClinicalTrials.gov ID: NCT00676897). Adult patients with suspected or confirmed infection and the need for vasopressor support were included in the initial trial. For the current analysis, blood specimens were analyzed for plasma CoQ10 and low-density lipoprotein levels. The relationship between CoQ10 levels and inflammatory and vascular endothelial biomarkers was assessed using Pearson or Spearman correlations.

Results:
28 samples from 14 patients were analyzed. CoQ10 levels were low with a median of 0.49 (IQR: 0.26 – 0.62) as compared to healthy control patients (CoQ10 = 0.95 umol/L +/- 0.29; p < 0.0001). Statin therapy had no effect on plasma CoQ10 levels over time (p = 0.13). There was a statistically significant relationship between CoQ10 level and vascular cell adhesion molecule (VCAM) (r2 = 0.2; p = 0.008), tumour necrosis factor- (r2 = 0.28; p=0.004), interleukin (IL)-8 (r2 = 0.21; p= 0.015), IL-10 (r2= 0.18; p=0.025), E-selectin (r2= 0.17; p=-0.03), IL-1ra (r2 =0.21; p=0.014), IL-6 (r2=0.17; p=0.029), and IL-2 (r2=0.23; p=0.009). Adjusting for low-density lipoprotein (LDL) levels there was a statistically significant inverse relationship between CoQ10 and VCAM (r2 = 0.24; p = 0.01; Figure 3) and IL-10 (r2 = 0.24; p = 0.02).

Conclusions:
CoQ10 levels are significantly lower in patients with septic shock compared to healthy controls. CoQ10 is negatively associated with vascular endothelial markers and inflammatory molecules though this association diminishes when adjusting for LDL levels.

The complete article is available as a provisional PDF.

 

 

Vitamin C: A Potential Life-saving Treatment For Sepsis

Physicians caring for patients with sepsis may soon have a new safe and cost-effective treatment for this life-threatening illness. Research led by Dr. Karel Tyml and his colleagues at The University of Western Ontario and Lawson Health Research Institute have found that vitamin C can not only prevent the onset of sepsis, but can reverse the disease.

Sepsis is caused by a bacterial infection that can begin anywhere in your body. Your immune system goes into overdrive, overwhelming normal processes in your blood. The result is that small blood clots form, blocking blood flow to vital organs. This can lead to organ failure. Babies, the elderly and those with weakened immune systems are most likely to get sepsis. But even healthy people can become deathly ill from the disease.

According to Dr. Tyml, a professor at Western’s Schulich School of Medicine & Dentistry, patients with severe sepsis have a high mortality rate, nearly 40 percent, because there is no effective treatment.

“There are many facets to sepsis, but the one we have focused on for the past 10 years is the plugging of capillaries,” says Dr. Tyml. Plugged capillaries prevent oxygenation and the supply of life-supporting materials to your organ tissue and stop the removal of metabolic waste product. Plugged capillaries are seen in organs of septic patients. These organs may eventually fail, leading to multiple organ failure and death. Dr. Tyml’s lab was the first to discover this plugging by using intravital microscopy, a technique Dr. Tyml pioneered in Canada.

According to Dr. Tyml’s most recent publication, oxidative stress and the activated blood clotting pathway are the major factors responsible for the capillary plugging in sepsis. Through his research, Dr. Tyml has discovered that a single bolus of vitamin C injected early at the time of induction of sepsis, prevents capillary plugging. He has also found that a delayed bolus injection of vitamin C can reverse plugging by restoring blood flow in previously plugged capillaries.

“Our research in mice with sepsis has found that early as well as delayed injections of vitamin C improves chance of survival significantly,” explains Dr. Tyml. “Furthermore, the beneficial effect of a single bolus injection of vitamin C is long lasting and prevents capillary plugging for up to 24 hours post-injection.”

Dr. Tyml and his colleagues are eager to find appropriate support to move this research from the bench to the bedside to see if these findings translate to patients with sepsis.

The potential benefit of this treatment is substantial. “Vitamin C is cheap and safe. Previous studies have shown that it can be injected intravenously into patients with no side effects,” says Dr. Tyml. “It has the potential to significantly improve the outcome of sepsis patients world-wide. This could be especially beneficially in developing countries where sepsis is more common and expensive treatments are not affordable.”
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