By Aaron W. Jensen, Ph.D.
ave you ever noticed that even as we try to simplify our
everyday lives, our stress levels continue to escalate? Maybe that’s because
our fast-paced lifestyles are inundated with mundane but insistent tasks—car
repairs, grocery shopping, mowing the lawn, visiting the gym, kids’ piano
lessons and soccer practice, cooking the evening meal, doctor and dentist
appointments . . . . The list of things we need to accomplish daily seems
endless. Each task takes a certain amount of time and patience—and when you’re
running low on both of those, daily life can be mighty stressful. Some days are
worse than others. Some days, in fact, you just want to holler, “Calgon, Take
Me Away!”*
Stress Is Inescapable
The stresses that engulf us take different forms. The most
common and significant ones are physical, social, and work-related stresses,
but other factors also contribute to our daily stress levels, such as noise,
insomnia, anxiety, and depression. Even solar ultraviolet radiation,
environmental toxins (both chemical and biological), and air pollution can
raise your stress levels. One thing is for certain: sources of stress are
everywhere. So it’s not surprising that your body has developed mechanisms for
coping with it.
When you’re overly stressed, your immune system becomes
compromised, your body’s functions become less efficient, and your mental faculties
begin to falter. Fortunately, however, your cells have built-in coping
mechanisms that are activated at such times. These processes are mediated by
the synthesis of special proteins—those endlessly versatile molecular
workhorses of the cell—to mobilize an effective and protective response.
Studying Stress with Molecular Chaperones
How do you study stress in a single cell in the laboratory?
Do you look for the little guy to wipe the sweat off his brow? Bite his lip in
concentration? Throw his hands up in despair? If only there were such telltale
signs, science would be a whole lot easier. Sadly, these clues don’t exist in
the molecular world, so scientists have had to devise other methods to study
the stress response in cells.
The classic method used to induce a stress response in cells
is to expose them to excess heat—but not too much, just a couple of degrees
does the trick—a process called heat shock. Shocking cells with heat (or other
stressors, such as cold, salt, toxins, or a variety of hormones) causes the
cells to increase their production of a specific set of proteins, inventively
called heat-shock proteins. But how does this help the cell survive stress?
Some heat-shock proteins are called chaperonins, a term that
hints at their function as molecular “chaperones.” In this role, they help
other proteins in the cell to maintain their normal structure (which is
typically very complex owing to the intricate folding of the long chain of
amino acids the protein is composed of). Heat and other stressors can cause
proteins to denature, which means that they lose their normal shape through an
unfolding of the chain. If this happens, the proteins also lose their normal
function, which is critically dependent on their shape, and they are ultimately
degraded in the cell.
Chaperonins help denatured proteins to fold back into their
normal shape and will even help to refold misshapen proteins. In so doing, they
restore functionality to the proteins, many of which are enzymes with critical
tasks to perform. Chaperonins thus help cells to survive under stressful
conditions and allow them to participate in normal metabolism, growth, and
maturation.
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Bacopa Activates Antistress Response
Scientists have long sought to understand the biological
mechanisms that help you cope with stress and to develop, if possible, ways in
which you can prompt your body to deal preemptively with the trials and
tribulations of everyday life. One exciting development in this area of
research centers on the Indian herb Bacopa monniera. Animal research shows that
this herb, which is found in wet, marshy areas throughout India, appears to
prime the stress-coping response in cells throughout the brain.
Traditional healing manuals from the ancient practice of
Ayurvedic medicine in India reveal that Bacopa has long been used as a memory
enhancer and anti-inflammatory agent. It has also been used to treat blood and
kidney disorders, as well as to reduce fever. Current research has focused on
the role that Bacopa plays in reducing stress, and a group of Indian
researchers has recently demonstrated that it activates an antistress response
in animals through the regulation of gene expression, the process that governs
protein synthesis.
How to Stress a Rat
The researchers isolated the principal active ingredients of
Bacopa—chemical compounds called bacoside A and bacoside B—from the root of the
plant and administered them to male rats that were then exposed to stress. They
used doses of 20 mg and 40 mg per kg of body weight, which correspond to 1500
mg and 3000 mg, respectively, for a 75-kg (165-lb) human. Because rats are not
subject to the same types of stress that we are—they don’t have auto accidents,
e.g., or a boss standing over them demanding a final report by the end of the
day—the researchers exposed them to stress in the form of physical restraint in
a cold chamber (41ºF) at a low oxygen level (equivalent to an altitude of
15,000 ft).
One group of rats was pretreated with Bacopa for 7 days
before exposure to the stress, and a control group was stressed similarly, but
without the Bacopa pretreatment. After about 2 hours of the stress, when the
animals’ core temperature had dropped to about 73ºF, they were removed and
immediately decapitated so that the levels of certain stress-response proteins
could be measured in different regions of their brains.
Antistress Proteins Perform Vital Functions
The proteins of interest were heat-shock protein 70 (Hsp70),
two cytochrome P450 enzymes (EROD and PROD),* and the enzyme superoxide
dismutase (SOD). These names may not roll trippingly off the tongue, but the molecules
perform some very important functions. Hsp70 helps cellular proteins retain or
regain their normal structure so that they remain functional. P450 enzymes,
such as EROD and PROD, protect the body from certain toxins by converting them
to less harmful compounds. And SOD dismantles especially destructive free
radicals called superoxides, converting them to harmless organic compounds plus
oxygen and hydrogen peroxide (the latter is inactivated by another enzyme,
glutathione peroxidase, by conversion to water and oxygen).
Antistress Activities of Bacopa
In response to stress, the levels of Hsp70 normally increase
in all regions of the brain. In stressed animals that had been pretreated with
Bacopa for 7 days, however, the increase in Hsp70 levels was significantly
less
than normal in certain regions of the brain, notably the cerebral cortex and
the hippocampus (a region of the brain that plays a central role in memory
processes). What does this mean? By producing less Hsp70 in response to stress,
those regions of the brain were indicating that the Bacopa had somehow made
them less susceptible to stress. In effect, the Bacopa tended to keep those
regions of the brain in a relatively nonstressed state even in the presence of
stress.
Bacopa had a different impact on the levels of the two P450
enzymes. In rats treated with Bacopa but not exposed to stress, the levels of EROD and PROD increased throughout the entire brain (although the increase in
EROD activity in the hippocampus was not statistically significant). This
suggests that Bacopa tended to “prime” the brain for stress—in essence, the
brain stockpiled these protective enzymes so that it could better deal with
stress when it arose. Increased levels of the enzymes occurred most
dramatically in the cerebral cortex following Bacopa treatment.
Bacopa somehow made those
regions of the brain less
susceptible to stress. In effect,
it kept them in a relatively
nonstressed state even in
the presence of stress.
The data pertaining to SOD were more difficult to interpret,
because the factors affecting SOD levels and activity in brain tissue are more
complicated, and they vary in different regions of the brain even under normal conditions.
Nevertheless, the researchers were able to conclude that Bacopa treatment also
has a positive effect on SOD activity in the brain. In their words, “. . .
Bacopa helps in coping with the combined hypoxic, hypothermic, and
immobilization stress, which could lead to an onslaught of free radicals.” Put
in simpler terms, Bacopa treatment modulates SOD activity and prepares tissues
to weather attacks by free radicals that may otherwise cause a great deal of
damage to the brain’s neurons.
Bacopa Protects Certain Parts of the Brain
The Indian research suggests that Bacopa has protective
benefits on select regions of the brain. But why is this important? Researchers
have known for a long time that specific functions reside in specific regions
of the brain. For example, the largest part of the brain, the cerebrum, is
divided into two hemispheres—the right and the left—and controls many different
functions. The left hemisphere controls speech, reading, writing, logic, and
movement on the right side of the body. The right hemisphere is associated with
creative and artistic abilities and coordinates movement on the left side of
the body.* The hippocampus, on the other hand, is involved in various
“executive” skills, such as learning, memory, and general cognition.
The fact that Bacopa selectively protects regions of the
brain associated with memory and learning is not surprising if you consider
that this herb has long been used as a memory enhancer in Ayurvedic medicine,
which dates back over 2500 years. This healing tradition places particular
importance on the restorative properties of Bacopa. Western medicine is warming
to this herb as well, and a growing number of clinical trials support its
memory-enhancing effect.
Bacopa Enhances Learning and Memory
One particularly important study on Bacopa was performed in
Australia, using neuropsychological testing. These tests measure a number of
different cognitive skills, such as attention, memory consolidation, short-term
memory, problem solving, decision making, information processing, and verbal
learning. In all, 16 well-validated tests were administered to 46 healthy adult
subjects, starting at the outset of the study to establish baseline levels for
each individual. Each participant was given 150 mg of Bacopa extract
(equivalent to 3 g of the dried herb) twice daily (300 mg/day total) for 12
weeks. Neuropsychological performance was measured again at 5 weeks and 12
weeks.
The results demonstrated that Bacopa significantly improved
performance on specific tests, most notably those dealing with information
processing, verbal learning, and memory consolidation. The authors concluded
that Bacopa improves cognitive processes that depend on environmental input and
is especially important in learning and memory.
Bacopa for Good Brain Health
One of the most significant challenges to the health of
individual brain cells comes in the form of oxidative stress. Despite its
relatively small size, the brain consumes about 20% of all the oxygen that is
taken into the body in order to help power its many activities. Owing to this
gluttonous oxygen consumption, the brain is exposed to very high levels of
oxidative stress in the form of free radicals, which can do a great deal of
damage to the brain’s sensitive neurons in very little time.
The authors concluded that
Bacopa
improves cognitive
processes that
depend on environmental input
and is especially important in
learning and memory.
Since Bacopa arms our neurons with stress-protection
mechanisms that boost the levels of protective proteins, this ancient herb may
offer a strong defense against the ravages of oxidative stress. In these
stressful times, that sounds like a good recipe for protecting and enhancing
brain function. In a sense, you can think of Bacopa as a restorative trip to
the spa for the brain. What could be better?
References
- Chowdhuri
DK, Parmar D, Kakkar P, Shukla R, Seth PK, Srimal RC. Antistress effects of
bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide
dismutase and cytochrome P450 activity in rat brain. Phytother Res
2002;16:639-45.
- Stough C,
Lloyd J, Clarke J, Downey LA, Hutchison CW, Rodgers T, Nathan PJ. The chronic
effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects.
Psychopharmacology 2001;156:481-4.
Dr. Jensen is a cell biologist who has conducted research in
England, Germany, and the United States. He has taught college courses in
biology and nutrition and has written extensively on medical and scientific
topics.
Taken from life-enhancement.com
