Aubrey de Grey: Don’t Make Peace with Aging; Anti-Aging Isn’t Science Fiction

Aging Process

Renowned researcher Aubrey de Grey, PhD, has a few things to say about the aging process.

“It is no longer acceptable to make your peace with aging.”

“The fact is that aging is really a very ghastly thing, and we’ve known that for a long time. Twenty years ago, it certainly did make sense to make one’s peace with aging because we didn’t have a plan to do anything about it in the foreseeable future. But now, if you take that attitude, then what you are doing is slowing down the research. You are slowing down the enthusiasm, the urgency of society that needs to exist in order that the remaining scientific and biomedical research that needs to be done to get these therapies in place can be done as quickly as possible, and that the maximum number of lives can be saved.”


Aging: Strategies for Engineered Negligible Senescence

Dr. de Grey is the Chief Science Officer of SENS (Strategies for Engineered Negligible Senescence) Research Foundation, a California-based biomedical research charity that, according to its website, is transforming the way the world researches and treats age-related disease. He’s also vice president of new technology discovery at Age-X Therapeutics.

Aging: Science Versus Technology

To understand aging well enough to be able to do something about it, it needs to be characterized. We need to determine what is different about the microscopic molecular and cellular structure of an older person relative to a younger person. Although difficult to do, these changes can be repaired to return the structures to the way they were at an earlier age.1 “You don’t need to understand how it got that way,” Dr. de Grey noted.

The need to know why phenomena occur is the province of scientists. “Scientists are all about testing hypotheses and understanding nature for the sake of understanding it,” Dr. de Grey explained. “But I’m not thinking about it from a scientific perspective, I’m thinking about it from a technological perspective.”

Medicine is a branch of technology. Medicine doesn’t necessarily try to understand nature but to manipulate it. To accomplish this, a certain amount of understanding is required, but there is a point at which we understand enough to carry out our goals. “And that’s where I’m saying we’re already at in regard to aging,” Dr. de Grey said.

Aging: Cells and Molecules

To address aging-related changes, one needs to examine cells. People can have too many, as in the case of cancer, or not enough. Cells also need to be studied at a molecular level. Even though cells may be present in the right number, there may be things going wrong within a cell, such as the accumulation of waste products or mutations. These problems can additionally occur outside of the cells in the matrix that holds the cells together in a structure that allows us to operate.

Mutations can occur in the DNA that resides in the cell’s nucleus or in its mitochondria, which are the cells’ energy-producing organelles. They’re the place where oxygen is combined with nutrients to extract their energy. This process creates a significant number of free radicals that damage mitochondrial DNA, with the result that it accumulates mutations at a more rapid rate compared with nuclear DNA.

To address this aging-related problem, Dr. de Grey and his colleagues have revived an idea that was suggested over 30 years ago, which is to insert backup copies of mitochondrial DNA into nuclear DNA where it’s less subject to free radical attack. An experiment in this area was recently published following more than a decade of research.2

Rejuvenation Versus Aging Retardation

Twenty years ago, Dr. de Grey suggested that rejuvenating the body might be easier than slowing down the rate at which the body accumulates damage. At that time, the idea wasn’t well received, but now the feeling among many scientists is that this approach is tenable, and the growing influx of capital into this area highlights the enthusiasm of the investment community to partner with researchers in tackling these challenges.

“Now is the time to stop making your peace with aging,” Dr. de Grey urged. “Now is the time to let yourself get your hopes up, to get emotionally invested in this and not to think about this as science fiction anymore.”

Like what de Grey has to say? Listen to the Live Foreverish podcast with Life Extension’s Dr. Michael Smith and his guest Aubrey de Grey, as they discuss Aging, by visiting LiveFOREVERish.com.

If you like what you hear, please take a moment to give Live Foreverish a 5-star rating on iTunes!

For more information about Aubrey de Grey’s research, visit www.sens.org

References

  1. Vijg J et al. Gerontology. 2014;60(4):373-80.
  2. Boominathan A et al. Nucleic Acids Res. 2016 Nov 2;44(19):9342-9357.

Evolution of Fitness in Humans: The Sedentary Shift

There’s a growing recognition of the harm incurred by prolonged inactivity (sedentary lifestyle) and the resulting lack of fitness. When did it become so common to lead a sedentary life? Humans weren’t always like this, what happened? Discover how the shift to a sedentary lifestyle came about and explore fitness trends that anyone can do, especially if you are wanting to stay fit outside of having a gym membership.

Fitness Trends Over Time

Evolution of Fitness in Humans

From the time of prehistoric hunter-gatherers, humans have engaged in vigorous physical activity as a matter of survival.

In 2004, research published in the journal Nature concluded that “endurance running is a derived capability of the genus Homo, originating about 2 million years ago, and may have been instrumental in the evolution of the human body form.”1

Changes in Fitness Routines Throughout History

Two hundred years ago, the majority of the American work force was employed in agriculture, which involved hours of monotonous heavy labor.

The Industrial Revolution lured many men, women, and children from farms to factories, yet labor was still often brutally demanding.

The relief from dangerous and exhausting physical drudgery was a boon to humankind. Yet the rise of desk jobs, along with such developments as television and computers that capture much of our spare time, has resulted in a large portion of the population spending most of its waking hours in a seated position. Decreased physical demands have lowered our caloric requirements, which, when combined with overconsumption of sugar and saturated fat, has contributed to the alarming prevalence of overweightness and obesity in the United States. According to the Centers for Disease Control and Prevention, more than 70% of Americans are now overweight or obese.2

Beginning in the 1950s, our need for regular exercise became evident. From Jack LaLanne’s TV fitness program, to Jane Fonda’s workout videos of the ’80s, to the exercise trends of the present day, there has been a continuously expanding awareness of physical activity as an essential component of a healthy lifestyle.

What’s more, the body of scientific evidence confirming the harm of prolonged inactivity and the benefit of regular exercise has exploded during the past decade.

For example:
  • Among 165,087 participants in the NIH-AARP Diet and Health Study, the risk of dying during a 6.6-year period was 28% greater among those who watched five or more hours of television per day compared to adults who watched less than three hours.3
  • In a study involving three U.S. population samples that included a total of 61,141 people, those who perceived themselves as less active than others had as much as a 71% greater risk of dying than those who perceived themselves as more active during follow-up periods of up to 21 years.4
With all the widely publicized evidence available, why don’t people exercise? Most individuals cite time constraints as their main excuse. But could it be that the mind rebels against the thought of an hour on a boring treadmill or endless, repetitive calisthenics?

In that case, how about participating in some of the fun, exotic fitness trends of the day? If you’re tired of the gym, try something you’ve never even thought about doing.

Think Outside the Box - Fitness Trends

No Gym Membership? No Problem!

Simple Fitness Trend: Dance like no one’s watching

Dancing to an energetic beat can get you moving like nothing else. Flamenco, belly dance, Zumba, and Bollywood-style dancing are joyful and energizing. If you’re adventurous, try pole dancing or even aerial dance.

Martial Arts Fitness Trends: Defend yourself

Boxing, karate, jiu–jitsu, and other martial arts are not only challenging forms of exercise but can also help you develop more confidence.

Outdoor Fitness Trend: High adventure

Scuba diving, hiking in an exotic locale, kayaking, rock climbing (outdoor or indoor), learning to surf—the possibilities are breathtaking!

Family Fitness Trends: Can’t get away?

A mini trampoline provides a low impact workout surface to enjoy the benefits of plyometrics (jump training) to the beat of your favorite tunes.

Adopting a dog from your local shelter will leave you with no excuse to get outside and walk, rain or shine. If you’ve never experienced the joy of animal companionship, now’s the time!

If you have children, try getting the whole family involved in something they really enjoy, such as bicycling or swimming.

The Bottom Line
Changes to lifestyle and work patterns over time have impacted the amount of physical activity people are getting. And research confirms this decline in physical activity has had a negative impact on health and longevity.

Exercise doesn’t have to be exhausting or boring. By engaging in enjoyable activities that challenge your mind as well as your body, you’ll look better, feel better, and have more energy.

Consult your physician before engaging in an exercise program if you have a health condition that may make a particular physical activity unsafe. Also remember that sound nutrition is a must to support your body in any physical endeavor.

References

  1. Bramble DM et al. Nature. 2004 Nov 18;432(7015):345-52.
  2. CDC/National Center for Health Statistics. May 2017. Available at: https://www.cdc.gov/nchs/fastats/obesity-overweight.htm
  3. Keadle SK et al. Int J Behav Nutr Phys Act. 2015 Dec 18;12:156.
  4. Zahrt OH et al. Health Psychol. 2017 Nov;36(11):1017-1025.

Rethinking Cholesterol and Heart Disease Risk with Cardiologist Michael Ozner, MD

You might think cholesterol alone is the key indicator of a healthy heart, but it’s not the “root” cause.

Learn how atherogenic lipoproteins become the deciding factor that leads to heart disease. Learn how to reduce your heart disease risk and the importance of omega-3 fatty acids.

Rethinking Heart Disease Risk and Cholesterol

What’s the most important factor in heart disease?

Cholesterol, right?

Not so fast, cautions cardiologist Michael Ozner, MD. “I think it’s very important that we understand the root cause of heart attacks.”

“It’s not cholesterol per se but, rather, these particles which we call atherogenic lipoproteins that carry cholesterol and triglycerides. Cholesterol actually serves a worthwhile purpose. It’s required for cell membranes, for steroid hormone development, for bile, and other things, and triglycerides are useful as energy source. We need them, and they can’t travel by themselves. They need to be carried.”

Dr. Ozner, who is the medical director of Wellness and Prevention at Baptist Health South Florida, likens lipoproteins to vehicles and cholesterol and triglyceride molecules to passengers. Traffic jams are caused not by too many passengers, but by too many vehicles which, when they have nowhere to go, take the exit ramp into the arterial wall where they can become trapped, modified, and oxidized. This process initiates the disease known as atherosclerosis. Atherosclerotic plaque is a collection of lipoproteins with their cholesterol and triglyceride cargo. Rupture of these plaques can lead to heart attack and stroke.1

Cholesterol and Atherogenic Lipoproteins

Understanding heart disease risk:

Apolipoprotein B (ApoB) is a component of some of the most atherogenic lipoproteins, including low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL) particles. Apolipoprotein A1 (ApoA1), on the other hand, is primarily associated with high-density lipoprotein (HDL) particles and is potentially helpful. Levels of ApoB and its ratio to ApoA1 have a stronger association with cardiovascular disease risk than the better-known lipoprotein cholesterol fractions.2 These factors can be evaluated with blood tests.

Heart Attack Misconceptions

While LDL cholesterol has long been considered the standard test to assess cardiovascular risk, LDL is not the root cause of atherosclerosis, according to Dr. Ozner. Elevated LDL-cholesterol levels contribute to risk but don’t always correlate with more important ApoB levels.

Individuals who are overweight with insulin resistance may have low LDL-cholesterol levels and think they’re not at risk of experiencing a cardiovascular event.3 A classic example of this phenomenon was the sudden death from heart attack of journalist Tim Russert: although doctors reported his LDL-cholesterol level was normal, an autopsy showed that he had advanced coronary artery disease.4

Heart Disease, Omega-3 Fatty Acids

Fortunately, most heart attack deaths are preventable. The importance of a healthy eating pattern, such as the Mediterranean diet, can’t be overemphasized.5 In contrast with the atherosclerosis-prone Western world is the Tsimane tribe of South America, who subsist by hunting, gathering, farming, and fishing. Although a high percentage of Tsimane have intestinal parasites triggering systemic inflammation, this tribe has one of the lowest levels of coronary artery disease of any population on record.6 Among many protective factors, the tribe’s intake of omega-3 fatty acids from the fish they harvest could be one of the most important. Consuming a high amount of marine omega-3 fatty acids, which include EPA and DHA, promotes cardiometabolic health; helps maintain normal triglyceride levels, heart rhythm, and blood pressure; and lowers inflammation.7-9

In one randomized, controlled trial, EPA combined with a statin drug was associated with greater regression of coronary plaque than drug therapy alone.10 This suggests that omega-3 supplementation may add to the reduction in risk of a cardiovascular event for those undergoing statin therapy. Assessment of omega-3 blood levels using the Omega-3 Index test can help guide appropriate omega-3 fatty acid intake.11



“For half a century, a high level of total cholesterol or low-density-lipoprotein cholesterol has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention,” noted a worldwide group of physicians in a recent review. “In our analysis of three major reviews that claim the cholesterol hypothesis is indisputable and that statin treatment is an effective and safe way to lower the risk of CVD, we have found that their statements are invalid, compromised by misleading statistics, by exclusion of unsuccessful trials, by minimizing the side effects of cholesterol lowering, and by ignoring contradictory observations from independent investigators.”12


Elevated LDL Cholesterol

Why this is not the sole factor for determining heart disease risk:

Elevated LDL cholesterol is one of many factors that have been associated with cardiovascular disease but according to many experts in the field, it’s not the most important one. The good news is that cardiovascular disease is largely preventable with a combination of lifestyle factors that may protect against a number of other diseases prevalent in our era.

Intrigued by what Dr. Ozner has to say? Visit LiveFOREVERish.com and listen to the Live Foreverish podcast of Life Extension®’s Dr. Michael Smith, with featured guest Michael Ozner, MD, who is medical director, Wellness and Prevention, Baptist Health South Florida, as they discuss “Cholesterol and Heart Disease Risk.”

If you like what you hear, please take a moment to give Live Foreverish a 5-star rating on iTunes!

References:


  1. Linton MF, Yancey PG, Davies SS, et al. The Role of Lipids and Lipoproteins in Atherosclerosis. [Updated 2015 Dec 24]. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK343489/
  2. Sandhu PK et al. J Appl Lab Med. 2016 Sep;1(2):214-29.
  3. Lim Y et al. Endocrinol Metab (Seoul). 2015 Jun;30(2):208-15.
  4. Lavie CJ et al. Ochsner J. 2008 fall;8(3):108-13.
  5. Torres N et al. Arch Med Res. 2015 Jul;46(5):408-26.
  6. Kaplan H et al. Lancet. 2017 Apr 29;389(10080):1730-1739.
  7. Mozaffarian D, Wu JH. Am J Coll Cardiol. 2011 Nov;58(20):2047-67.
  8. Bird JK et al. Nutrients. 2018 Jun;10(6):pii:E775.
  9. Arca M et al. Nutr Metab Cardiovasc Dis. 2018 Mar;28(3):197-205.
  10. Watanabe T et al. J Cardiol. 2017 Dec;70(6):537-544.
  11. von Schacky. Nutrients. 2014 Feb;6(2):799-814.
  12. Ravnskov U et al. Expert Rev Clin Pharmacol. 2018 Sep 10.

Michael T. Murray, ND: You’re Only as Healthy as Your Gut

Hippocrates asserted that all health, as well as all disease, begins in the gut. Natural health author and Bastyr University Board of Regents member Michael T. Murray, ND, wholeheartedly agrees.

“I really think that in this day and age, we need to rediscover the importance of gut health,” this modern-day Hippocrates affirmed.

There’s a growing awareness in both the scientific and lay communities of the importance of the microorganisms that reside in the intestinal tract. This microbiome plays a significant role not only in gut health, but also in mood, cognitive function, metabolism, and more. Our society faces an urgent need to focus on how we can improve digestion and build a healthy microbiome.

Signs and Symptoms

Signs of poor gut health range from gas, bloating, indigestion, heartburn, and constipation to more serious conditions. The deterioration of digestive health that is evident today can be blamed on a combination of factors, including consumption of poor quality food and the indiscriminate use of proton pump inhibitors (PPIs) that impair nutrient absorption — drugs that Dr. Murray predicts will remain on the market for only another 5 to 10 years.1-3

Excess stomach acid that PPIs and other drugs suppress may not always be a culprit in the development of gastrointestinal (GI) symptoms. If symptoms occur within 15 to 30 minutes after eating, the problem could be that the stomach isn’t producing enough acid. For these individuals, digestive enzymes and betaine hydrochloride supplements may help support healthy digestion.4, 5

Digestion and Enzymes

Food intolerance is a condition one hears a lot about these days. In many cases, it isn’t so much the type of food that’s consumed but the impairment of the ability to break down the food that’s the culprit. Inadequate secretion of digestive enzymes or poor digestive enzyme activity share some of the blame. With aging, the body’s production and secretion of digestive enzymes can decline.6 Supplementation with high-potency digestive enzymes can come to the rescue by breaking down offending food particles.7

Dr. Murray believes that many of the symptoms people seek to treat with probiotic supplements would be better addressed by digestive enzymes. Probiotics are critical when it comes to overall health, immune function, and more,8 but they don’t digest food. Poor digestion can lead to an imbalance in the gut bacteria in favor of those that thrive in the presence of undigested proteins and carbohydrates.9,10 The focus should be on improving digestion to feed the beneficial bacteria. With the proper breakdown of food, we naturally encourage a healthier microbiome.

The approach to digestive health is based upon a failed model. It’s founded on suppressing symptoms and not addressing their underlying cause. It’s not one that promotes health.

To the many Americans who suffer from GI symptoms,11 Dr. Murray offers reassuring words: “There are answers out there.”

Like what Dr. Murray has to say? Listen to the Live Foreverish podcast of Life Extension’s Dr. Michael Smith, with featured guest Michael T. Murray, ND, chief science officer of Enzymedica, as they discuss gut health, by visiting LiveFOREVERish.com.

If you like what you hear, please take a moment to give Live Foreverish a 5-star rating on iTunes!

References

  1. Hess MW et al. Aliment Pharmacol Ther. 2012 Sep;36(5):405-13.
  2. Lam JR et al. JAMA. 2013 Dec 11;310(22):2435-42.
  3. Lam JR et al. Gastroenterology. 2017 Mar;152(4):821-829.e1.
  4. Kines K et al. Integr Med (Encinitas). 2016 Aug;15(4):49-53.
  5. Majeed M et al. J Med Food. 2018 Aug; doi: 10.1089/jmf.2017.4172.
  6. Roxas M. Altern Med Rev. 2008 Dec;13(4):307-14.
  7. Felicida-Reynaldo RF, Kenneally M. Medsurg Nurse. 2016 May-June;25(3):182-5.
  8. George Kerry R et al. J Food Drug Anal. 2018 Jul;26(3):927-39.
  9. Carding S et al. Microbial Ecol Health Dis. 2015 Feb;26:26191.
  10. Gericke B et al. Mol Cell Pediatr. 2016 Dec;3(1):2.
  11. Drossman DA et al. Dig Dis Sci. 1993 Sep;38(9):1569-80.

6 Healthful Reasons to Eat Nutmeg

Nutmeg, while not a type of nut, is the seed of Myrista fragrans, a tree that grows in Indonesia. The seed is covered with a skin known as mace which, like nutmeg, is also used as a spice.

Although strongly associated in the West with holiday treats like pumpkin pie and eggnog, nutmeg has a medicinal use — particularly in the East, where it is used for toothache, infection, asthma, and rheumatic pain.

Related Article: Cinnamon and Blood Sugar

In traditional Chinese and Arab medicine, nutmeg is used to treat gastrointestinal disease, including diarrhea. Recent research has shown that nutmeg helps with disordered lipids, elevated blood glucose, heart tissue damage and liver toxicity.

Nutmeg contains phytochemicals that provide significant antioxidant activity, including eugenol, sabinene, elemicin, α-pinene, β-pinene, limonene, and more. Eugenol and isoeugenol have been found to play a major role in nutmeg’s ability to inhibit platelet aggregation.1

Effects on Inflammation

Nutmeg’s anti-inflammatory property and analgesic effect, as confirmed in experimental research, suggests a use as a chronic pain reliever.2 In addition to inhibiting lipid peroxidation, extracts of nutmeg have demonstrated an ability to inhibit the cyclooxygenase enzymes COX-1 and COX-2, which are involved in inflammation.3

Gastrointestinal Help

A study involving rats with induced diarrhea found that two weeks of an orally administered extract that contained nutmeg significantly reduced diarrhea scores and weight and number of wet stools, while improving signs of intestinal damage. Further investigation led the researchers to conclude that the extract’s antidiarrheal effect may, in part, be the result of the regulation of hormones involved in the maintenance of fluid and electrolyte levels as well as the enhancement of sodium ions and water.4

Anti-microbial Activities

Nutmeg’s antifungal effect was demonstrated in a study that evaluated its effects against Candida albicans, the cause of oral thrush and vaginal yeast infections. In a comparison with the antifungal drug nystatin, nutmeg extract displayed marked anti-Candida activity, suggesting its use as an adjunct to conventional therapy.5 Nutmeg also has an antibacterial effect, which may be attributable in part to its sabinene content. One study suggested that sabinene might be more potent than ciprofloxacin, the standard drug treatment for Salmonella typhimurium, and concluded that the compound might be a safe alternative to treat infection and fight drug resistant bacteria.6

Malabaricone C from nutmeg has shown potential against Streptococcus pneumoniae via an ability to inhibit enzymes that facilitate bacterial colonization.7 An investigation of nutmeg extracts in oral bacteria revealed activity against Streptococcus mutans ATCC 25175, Streptococcus mitis ATCC 6249, Streptococcus salivarius ATCC 13419, Aggregatibacter actinomycetemcomitans ATCC 29522 and Porphyromonas gingivalis ATCC 33277.8

Neurological Effects

Research indicates a neuroprotective effect for nutmeg. A study suggests that some lignans may cross the blood-brain barrier, the structure that prevents the entry into the brain of many potentially beneficial, as well as harmful, substances.9 The compound macelignan has been shown in vitro to protect neurons that produce dopamine, which degenerate in Parkinson’s disease.10 In the rat hippocampus (an area of the brain that is important for memory and emotion), nutmeg increased the neurotransmitters serotonin, norepinephrine and dopamine in comparison with a control group.11 

In neurons deprived of oxygen, the nutmeg compound myristicin enhanced cell viability by inhibiting apoptosis (programmed cell death).12 Myristicin additionally inhibited malondialdehyde (a compound that is marker of oxidative stress) and upregulated the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase. Nutmeg compounds have also demonstrated activity against acetylcholinesterase, an enzyme that breaks down the neurotransmitter acetylcholine.13

Cancer Research

A water extract of nutmeg seeds has been shown to suppress the growth of human colon cancer cells and reduced tumor growth in mice that received transplanted lung cancer cells. 14 The researchers found that nutmeg inhibited cancer growth and cancer metabolism by inhibiting the activity of a key enzyme responsible for cancer metabolism regulation known as lactate dehydrogenase. In a mouse model of colon cancer, nutmeg reduced the formation of intestinal tumors. In this animal model, nutmeg attenuated the levels of uremic toxins, which are likely produced by the gut microbiota, and decreased intestinal tumorigenesis.

Nutmeg-treated mice had decreased interleukin-6 levels and normalized dysregulated lipid metabolism. These findings suggested that, at least in part, the uremic toxins were responsible for the metabolic disorders that occur during tumorigenesis. Moreover, these findings demonstrate a potential biochemical link among gut microbial metabolism, inflammation, and metabolic disorders, and suggest the possibility to develop colon cancer chemoprevention strategies by modulating the gut microbiota and lipid metabolism using dietary interventions or drugs.15

Liver Research

Researchers from China recently studied nutmeg’s liver-protective effects.16 They found that nutmeg extract protected against liver damage induced by a toxic compound in mice, as revealed by recovery of liver enzymes, and less oxidative stress and inflammation in the liver. Gene expression analysis determined that the protective effect was the result of modulation of the peroxisome proliferator-activated receptor alpha (PPAR alpha), which regulates the transcription of genes involved in fatty acid oxidation and transport. The researchers discovered that myrislignan, a neolignane in nutmeg, was also significantly protective against liver injury.

The lignan nectandrin B has been shown to protect liver cells against oxidative injury and suppress liver cell fat accumulation, possibly by mechanisms that include AMPK activation.17,18

Will Nutmeg Become a Drug?

“Nutmeg is a valued kitchen spice that has been used for centuries all over the world,” Ehab A. Abourashed and Abir T. El-Alfy of Chicago State University wrote in a recent review. The authors highlight that, as a source of diverse secondary metabolites with potential for drug discovery, nutmeg needs to receive more attention as a resource for developing new drug entities of benefit humanity.19

References

  1. Janssens J et al. J Ethnopharmacol. 1990 May;29(2):179-88.
  2. Zhang WK et al. Food Nutr Res. 2016 Apr 26;60:30849.
  3. Zhang CR et al. Nat Prod Commun. 2015 Aug;10(8):1399-402.
  4. Xiong R et al. Biomed Pharmacother. 2018 Feb;98:834-846.
  5. Iyer M et al. J Indian Prosthodont Soc. 2017 Jul-Sep;17(3):267-272.
  6. Vimal A et al. 3 Biotech. 2017 Aug;7(4):258.
  7. Park JY et al. Bioorg Med Chem Lett. 2017 Jul 15;27(14):3060-3064.
  8. Shafiei Z et al. Evid Based Complement Alternat Med. 2012;2012:825362.
  9. Wu N et al. Molecules. 2016 Jan 22;21(2):134.
  10. Kiyofuji K et al. Eur J Pharmacol. 2015 Aug 5;760:129-35.
  11. Plaingam W et al. J Tradit Complement Med. 2017 Jun 15;7(4):538-552.
  12. Zhao Q et al. Mol Med Rep. 2017 Apr;15(4):2280-2288.
  13. Cuong TD et al. Nat Prod Commun. 2014 Apr;9(4):499-502.
  14. Kim EY et al. Am J Chin Med. 2016;44(5):1063-79.
  15. Li F et al. J Proteome Res. 2015 Apr 3;14(4):1937-46.
  16. Yang XN et al. J Proteome Res. 2018, 17(5):1887-1897.
  17. Song JS et al. Toxicol Appl Pharmacol. 2016 Sep 15;307:138-149.
  18. Choi DG et al. Pharmazie. 2015 Nov;70(11):733-9.
  19. Abourashed EA et al. Phytochem Rev. 2016 Dec;15(6):1035-1056.

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