A native Mediterranean mushroom found to protect the liver from disease

Image: A native Mediterranean mushroom found to protect the liver from disease

People with high blood sugar exhibit high lipid levels brought about by excessive intake of fatty foods — a condition called hyperlipidemia. When left untreated, hyperlipidemia can pave the way for other diseases like atherosclerosis and fatty liver. If certain foods can cause hyperlipidemia, there are also foods that can prevent it. A study, published in BMC Complementary and Alternative Medicine, revealed that the edible mushroom Pleurotus eryngii can reduce lipid levels and protect the liver.

In hyperlipidemic patients, there is an increase in the bad cholesterol, low-density lipoprotein cholesterol (LDL-C), while the good high-density lipoprotein cholesterol (HDL-C) levels are reduced. Altered lipid levels have been shown to inhibit the activity of antioxidant enzymes in the body, which causes free radicals to build up and induce oxidative damage. Since the liver serves as a storage for excess fat, it is susceptible to damage caused by the fat buildup and oxidative stress.

There are more than 95 million people that have been diagnosed with hyperlipidemia in the U.S. alone, which is why this problem should immediately be addressed. Although there are prescription drugs for treating hyperlipidemia, these are associated with adverse side effects and are not advised for long-term use. Because of this, people are now turning to natural antihyperlipidemic substances.

One of the potential alternatives that researchers considered is P. eryngii, a mushroom that originated from the Mediterranean region. Previous studies have shown that P. eryngii contains many bioactive compounds, including polysaccharides, sterols, and peptides. Among these, polysaccharides were shown to be the most potent since it has antioxidant, anti-aging, antivirus, and anti-lipid peroxidation properties. Aside from these, polysaccharides are also highly stable, water-soluble, and non-toxic, which makes them suitable for medicinal applications. Although there have been studies regarding the antihyperlipidemic effects of polysaccharides from P. eryngii, none of these focused on exopolysaccharides.

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In this study, the researchers conducted both in vitro and in vivo evaluations of exopolysaccharides from P. eryngii. For the in vitro studies, they first determined what monosaccharides were present in the samples. They then proceeded to evaluate antioxidant activity based on free radical scavenging activity and reducing power. Results showed five different monosaccharides were present in exopolysaccharides. These were arabinose, xylose, mannose, galactose, and glucose. The researchers also observed that the exopolysaccharides have potent antioxidant activity. This is important since antioxidants prevent oxidative stress from inducing inflammation.

The in vivo experiments were performed on Kunming strain mice that were perfused with high-fat emulsion than the exopolysaccharides. After 28 days of this treatment, the liver and serum samples were collected from the mice and subjected to biochemical and histopathological analysis. Aside from these, the toxicity of exopolysaccharides was also determined. The results showed that without the exopolysaccharide treatment, the mice experienced an increase in body weight and liver weight, which could be a sign of fatty liver. They also had elevated triglyceride, total cholesterol, and LDL-C levels while HDL-C was reduced. Additionally, the activity of antioxidant enzymes was significantly reduced. In mice perfused with exopolysaccharides, all of the aforementioned effects of the high-fat emulsion were improved, proving that the exopolysaccharides can be used to treat hyperlipidemia.

“[Exopolysaccharides] exhibited potential and impressive prevention effects on high-fat diet-induced hyperlipidaemia in mice that were similar to those of the prophylactic agent simvastatin, demonstrating that polysaccharides can be exploited as potential natural drugs and functional foods for the prevention and treatment of hyperlipidaemia,” the researchers concluded.

Based on these results, it can be determined that exopolysaccharides from P. eryngii can be utilized for the treatment of hyperlipidemia since it has antioxidant, antihyperlipidemic, and hepatoprotective properties. These properties make it a good alternative for harmful prescription drugs.

Children with Psoriasis Carry High Comorbidity Risks

Children with psoriasis are significantly more likely to develop obesity, hyperlipidemia, hypertension, diabetes, metabolic syndrome, polycystic ovarian syndrome, liver disease, and elevated liver enzymes than are children without the disease, according to a retrospective review of insurance claims data.

These risks are independent of obesity status: in non-obese children with psoriasis, the risk of comorbidities was 40% to 75% higher than in children without psoriasis, reported Megha M. Tollefson, MD, of the Mayo Clinic in Rochester, MN, and colleagues. But even in children without psoriasis, obesity was a much stronger contributor to comorbidities.

“In recent years, it has become increasingly clear that psoriasis is more than a ‘skin-deep’ condition and that it may frequently be associated with other systemic comorbidities, even in children,” the researchers wrote online in JAMA Dermatology. “While the association in adult patients is well established, the patterns and predictors of the risk of comorbidities in children with psoriasis are still not clear.

“There is mounting evidence that children with psoriasis are more likely to be obese than children without psoriasis, but this finding begs the question of whether the systemic comorbidities that are seen in children with psoriasis are attributable to obesity, or whether psoriasis is actually an independent risk factor for these comorbidities.”

In this study of claims from Optum Laboratories Data Warehouse, a Massachusetts-based Mayo Clinic partner, the researchers studied de-identified records of 29,957 children with psoriasis (affected children) and 29,957 children without psoriasis, matched for age, sex, and race, from 2004 through 2013.

The children, all under age 19, were divided into four groups:

  • Non-obese without psoriasis (reference cohort)
  • Non-obese with psoriasis
  • Obese without psoriasis
  • Obese with psoriasis

The average age of the children was 12.0, and 53.5% of the total were girls. At baseline, more affected children were obese than non-obese (2.9% versus 1.5%; P<0.001).

The average follow-up period for both groups was about 3 years. During this time, pediatric psoriasis patients were significantly more likely to develop comorbidities than those without psoriasis, with non-alcoholic liver disease, diabetes, and hypertension showing the highest risks.

Among non-obese children, the risk of comorbidities was significantly higher in those with psoriasis; these included elevated lipid levels (HR 1.42), hypertension (HR 1.64), diabetes (HR 1.58), metabolic syndrome (HR 1.62), polycystic ovarian syndrome (HR 1.49), non-alcoholic liver disease (HR 1.76), and elevated liver enzyme levels (HR 1.46).

Even in children without psoriasis, obesity was a much stronger contributor to comorbidities, carrying an 18-fold higher risk of non-alcoholic liver disease, a 16-fold higher risk of metabolic syndrome, a seven-fold higher risk of hypertension, a six-fold higher risk of hyperlipidemia, an almost three-fold higher risk of diabetes, and a 2.3-fold higher risk of elevated liver enzyme levels than the reference group; there was also a six-fold higher risk of polycystic ovarian syndrome in girls.

When the researchers analyzed the interaction between obesity and psoriasis, they found none, suggesting that while both obesity and psoriasis contribute to the development of pediatric comorbidities, the effect is additive, not exponential.

Asked for her perspective, Amy Paller, MD, chair of the Department of Dermatology at Northwestern Medicine Feinberg School of Medicine in Chicago, who was not involved with the study, noted that several studies have clearly demonstrated the association of obesity and pediatric psoriasis, and a large recent study also linked a high waist circumference to height ratio to more severe pediatric psoriasis. “The association of a variety of other ‘metabolic syndrome’ comorbidities has been controversial, however, and whether it is the obesity or psoriasis itself that increases the risk remains unknown.

“While there are issues with the use of a claims database, especially given the frequent misdiagnosis of psoriasis by non-dermatologists, several metabolic-related disorders were shown to be significantly increased in risk,” she said, adding that the fact that the associations were seen even among non-obese psoriasis patients suggests that early systemic intervention might lower risks.

The study has several limitations, Tollefson and colleagues noted. For example, it relies on data from administrative claims, and the diagnoses were not confirmed by medical record review. Also of possible concern are undercoding and misclassification of comorbidities. Extremely obese children would be more likely to have a corresponding obesity code than those with a body mass index of 25 to 40, the researchers added. “The lower prevalence of obesity in our cohort than in some others suggests that obesity may have been undercoded as a whole, with the resulting contribution from psoriasis being slightly overestimated.”

In addition, systemic medications used to treat psoriasis potentially might have influenced the risk of some comorbidities.

Hyperlipidemia May Hike Risk of Allograft Rejection

Hyperlipidemia increases the risk of allograft rejection through at least two mechanisms, according to studies in mice.

“The most important clinical implication is that concomitant health conditions that exist in the transplant population have a profound effect on rejection and the ability to regulate rejection,” Dr. John Iacomini, from Tufts University School of Medicine, Boston, told Reuters Health by email. “It is likely that this will be the case for other diseases involving inflammation and immunity such as autoimmune disease, neurological disorders.”

Although hyperlipidemia affects 95% of organ transplant recipients, its effect on organ allograft rejection has not been investigated.

Dr. Iacomini’s team investigated the influence of hyperlipidemia on vascularized cardiac allografts in mice in two separate series of experiments designed to elucidate mechanisms behind hyperlipidemia-related allograft rejection.

The studies derived from the fact that co-stimulatory molecule blockade successfully induces allograft tolerance in mice but has not proven successful in the clinic. They reasoned that this result “might be due to limitations in our understanding of transplant rejection and acceptance that result from the use of animal models that do not capture health conditions present in the human transplant population.”

In the first study, they found that ApoE-deficient mice fed a diet resulting in hyperlipidemia showed accelerated rejection of cardiac allografts.

The researchers traced this accelerated rejection to increased IL-17 production in hyperlipidemic recipients and an increased frequency of T cells capable of responding to alloantigen in the absence of prior antigen exposure.

According to their June 16 American Journal of Transplantation online report, the finding that Th17 cells play a critical role in rejection when examined in the context of physiologic conditions in the transplant patient population “shifts the current paradigm by demonstrating that rejection must be studied in the context of conditions such as hyperlipidemia that play a previously undescribed role in altering rejection.”

The second study investigated the effect of hyperlipidemia on FoxP3+ regulatory T cells (Tregs), which play a key role in allograft tolerance.

Induction of hyperlipidemia in ApoE-deficient mice was associated with profound changes in Treg frequencies and populations. While there was an increase in FoxP3+ T cells, the increase did not come in the population known to contain functional Tregs.

Hyperlipidemia-induced reductions in the frequency of central Tregs were matched by increases in the frequency of effector Tregs, and hyperlipidemia brought other changes that resulted in defective Treg function.

Moreover, hyperlipidemia prevented tolerance induction using approaches that require Treg activity, such as co-stimulatory molecule blockade.

 “Long-term survival rates have not shown great improvement in the last 2 decades,” Dr. Iacomini said. “We believe that this may be related to the use of animal models that have been used to develop our canonical understanding of transplant rejection and tolerance. Typically, these models do not take into consideration health conditions that exist in the transplant population. By studying transplant rejection and tolerance in the context of one such condition, hyperlipidemia, we discovered that these conditions fundamentally change rejection and tolerance.”

“In the context of transplant patients, hyperlipidemia needs to be tightly controlled,” Dr. Iacomini said. “Given that a substantial number of transplant patients are hyperlipidemic, we need to develop new ways to control lipid levels and develop an understanding of how lipid levels alter immunity.”

Dr. Deirdre L. Sawinski and Dr. Jonathan S. Maltzman, from the University of Pennsylvania’s Perelman School of Medicine, Philadelphia, wrote an editorial related to these reports. Dr. Maltzman told Reuters Health by email, “The studies discussed in the editorial not only use genetic manipulation, but also emphasize that environmental factors can alter the response to organ transplantation. They suggest that we not only need to consider genetic, but also environmental (i.e., diet, etc.) factors.”

“These studies show that a high-fat diet impacts the immune response and skews it toward rejection and this suggests that avoidance of a high-fat diet in our transplant recipients may have benefits in terms of decreased rejection episodes in addition to known cardiovascular benefit,” Dr. Maltzman concluded.

“Further studies of the effect of diet (fat content, sodium content, etc.) and other modifiable factors on the immune response are critical for improving outcomes in transplantation — and these should be undertaken using both animal models and evaluating the effects in the clinical transplant setting,” he added.

Dr. Mandy L. Ford, scientific director of the Emory Transplant Center, Emory University, Atlanta, told Reuters Health by email, “While the study was done in a mouse model and more research in human patients is required, these findings raise the possibility that immunosuppressive regimens that are sufficient for controlling transplant rejection in normolipidemic patients may suboptimally limit alloimmunity in hyperlipidemic patients.”

“This study indicates that because anti-donor immunity is altered in the setting of hyperlipidemia, results obtained in normolipidemic animals may not be able to be extrapolated to patients with hyperlipidemia,” she said. “It highlights a real need to better reflect the metabolic characteristics of our transplant patient populations in experimental mouse models of transplantation.”