This document discusses circadian rhythms and how botanical adaptogens can be used to target the 24-hour circadian cycle. It begins by defining circadian rhythms as the body's internal 24-hour cycles that allow for adaptation to daily environmental changes. It then discusses the three main components of the human circadian clock system: the input pathways, central circadian clock, and peripheral clocks. Several botanicals are then presented that can be used to modulate the circadian rhythm and cortisol cycle, including holy basil, eleuthero, reishi, rhodiola, rhaponticum, licorice, cordyceps, ashwagandha, and magnolia. Dosages and times of day for application of each botan

1. Mary Bove, ND
July 12, 2023
Targeting the 24-Hour Circadian
Cycle with Botanical Adaptogens

2. • Dr. Bove is receiving compensation for
creating and presenting this webinar.
Disclaimer

3. • Internal manifestations of the solar day that permit adaptations to
predictable environmental temporal changes.
• 24-h rhythms are controlled by molecular clockworks within the brain
that are reset daily to precisely 24-h by exposure to the light–dark
cycle.
• A bidirectional relationship exists between mood disorders and
circadian rhythms.
Circadian Rhythms
Nature Reviews Neuroscience volume 20, pages49–65 (2019)

4. • The input pathways, which receive and relay exogenous cues to the
brain
• Light exposure (most “potent”), feeding times, physical activity, and sleep
habits
• A central circadian clock in the brain, which maintains the circadian
rhythm (“master clock”)
• Peripheral clocks within individual organs, which control the
physiologic, behavioral, and metabolic end responses
Three Essential Components of the
Human Circadian Clock System

5. • In humans, circadian nocturnal sleep-daytime wakefulness is
associated with changes in peripheral cytokines, cellular immune
functions, and endocrine influences.
• The interaction between the circadian sleeping/waking brain and the
cytokine-immune-endocrine system are integral to preserving
homeostasis.
Circadian Sleep/Wake Brain
http://dx.doi.org/10.1016/S1087-0792(99)90003-5

6. • Wide range of metabolic processes— including lipid metabolism,
glucose metabolism, oxidative phosphorylation, and detoxification
pathways
• Any desynchrony with each other or with the central clock, can
directly impact:
• Individual thoughts and behaviors
• Overall health
• Predilection for disease development
Peripheral Clocks

7. 7
https://www.non-24pro.com/physiology-of-non-24.php
Circadian Rhythms Affect All Organs and
Systems

8. Normal 24-hour Circadian Cortisol Cycle
Cortisol is released in a circadian
rhythm pattern. This means that the
levels of cortisol change based on
the time of day
Cortisol levels are highest in the
morning, decline sharply by noon,
flatten out in the afternoon, and
slightly decline before bed
This type of pattern suggests a
properly functioning Hypothalamic-
Pituitary-Adrenal (HPA) Axis

9. Mother Baby Rhythms
Rhythms of life: circadian disruption and brain disorders across the lifespan
Nature Reviews Neuroscience volume 20, pages49–65 (2019)

10. • Sleep disturbances and circadian disruptions are associated with
attention-deficit hyperactivity disorder (ADHD) and autism spectrum
disorders (ASDs).
• Inattentiveness, impulsivity and hyperactivity are associated with high
rates of co-occurring sleep problems and circadian alterations.
• Reductions in sleep quality, delays in circadian phase and evening
preference are consistently reported in children and adults with
ADHD and may be correlated with the severity of ADHD symptoms.
Circadian Disruptions
Nature Reviews Neuroscience volume 20, pages49–65 (2019)

11. • The behavioral health and psychiatric consequences of circadian
disruption by light at night are becoming increasingly apparent.
• Circadian rhythms can be disrupted by jet travel across time zones.
• Light at night has the potential to substantially alter physiology and
behavior via suppression of melatonin rhythm.
• Exposure to light at night could dysregulate the HPA axis, in turn
increasing the prevalence of cortisol-associated mood disorders
Light at Night and Screentime
Translational Psychiatry volume 10, Article number: 28 (2020)

12. • Human clinical data support a strong interaction between MDD and circadian processes.
• Symptoms of depression demonstrate diurnal variations; patients exhibit symptoms in a
morning-worse or evening-worse pattern.
• Disruptions of biological rhythms underlie hallmarks of MDD; specifically, alterations in
sleep/wake states (decreased latency to rapid eye movement sleep, concurrent with
increased rapid eye movement sleep and reduced slow wave sleep), social rhythms,
hormone rhythms (reduced amplitude in melatonin and cortisol rhythms), and body
temperature rhythms (reduced amplitude and increase in nocturnal body temperature)
are seen in patients with MDD.
• Clinical studies demonstrate that the severity of MDD is correlated with the degree of
misalignment of circadian rhythms
Circadian Disruptions
Translational Psychiatry volume 10, Article number: 28 (2020)

13. Neurodegeneration and the circadian clock:
“Here, we review the common circadian abnormalities observed in
ADs, PDs and HDs, and circadian-oriented interventions proposed as
treatments for these neurological disorders.”
Frontiers in aging neuroscience, 2017 - frontiersin.org
Circadian Rhythm Disruption

14. • Circadian system — A novel diagnostic and therapeutic target in
Parkinson's disease? Aleksandar Videnovic MD, MSc,Gregory L. Willis
PhD First published: 30 January 2016
https://doi.org/10.1002/mds.26509Citations: 65
• Alterations of the circadian system in Parkinson's disease patients;
Karim Fifel PhD; First published: 15 November 2016
https://doi.org/10.1002/mds.26865Citations
Parkinson's Disease

15. • Manage your exposure to light. Light is the strongest signal in the environment to help
reset your sleep-wake cycle. You may need more sunlight during the day and less
artificial light at night from TV screens and electronic devices. Artificial light can lower
your melatonin levels, making it harder to fall asleep.
• To move your sleep and wake times earlier, use the light box when you wake up in the
morning. This may also help reduce daytime sleepiness. This method may be used to
help treat delayed sleep-wake phase disorder, irregular sleep-wake rhythm disorder, and
jet lag disorder when you travel east.
• To move your sleep and wake times later, use the light box late in the afternoon or early
in the evening. This method may be used to help treat advanced sleep-wake phase
disorder, shift work disorder, and jet lag disorder when you travel west
Light to Reset
Circadian rhythm disruption and mental health
Translational Psychiatry volume 10, Article number: 28 (2020)

16. • Time of day
• Target system, organ, or gland
• Action and energetics of botanicals
• Duration of therapy
Botanical Application in Relationship to
the Circadian Rhythm
0800 1200 1700 2100
Hour of Sample
Collection
Salivary
Cortisol
0
0800 1200 1700 2100
Hour of Sample
Collection
Salivary
Cortisol
0

17. • Regulating adrenal and HPA axis communication
• Homeostasis of cortisol patterns & influences
• Glycemic regulation and stability
• Healthy sleep wake cycle
• Application of specific adaptogen agents in the 24-hour cycle
• Morning
• Night
• Daytime
Restoring the Adrenal 24-Hour Cycle

18. • Apply botanicals for modulating cortisol into the normal cortisol
circadian cycle.
• Supportive Adaptogens – Holy Basil, Eleutherococcus, Reishi,
• Revitalizing Adaptogens – Rhodiola, Rhaponticum, Licorice, Cordyceps
• Restoring Adaptogens – Withania, Magnolia, Mimosa
Cortisol and Botanicals
Adaptogen Dosing & Time of Day

19. MOA of Plant-originated Adaptogens
on Human Body
PMCID: PMC6240259
PMID: 30479654

20. • Adaptogen, antiviral, galactagogue, radioprotective, hypoglycemic,
anti-inflammatory, cortisol regulator
• Enhancing metabolic functions and natural resistance
• Modulates innate stress response
• Reduces generalized anxiety
• Enhanced endurance
• Cortisol reducing compounds
• Ursolic acid, a constituent in Holy Basil, activity as an anti-
inflammatory and COX-2 inhibitor.
• Enhances the activity of glutathione S-transferase, a key enzyme in
detoxification
• 4-10 mls/day 1:5LE
• 250-1000 mg/d dry herb
Holy Basil - Ocimum sanctum

21. • Root, Araliaceae
• Immunotonic, adaptogen, neuro-protective, hepato-
protective, gastro-protective, anti-oxidant, anxiolitic
• Regulates blood sugar levels for hypo & hyper
• Effects of prolonged stress, fatigue, insomnia, depression,
post surgery/ trauma/ chemotherapy
• Normalizes leukocyte levels
• Improves reproductive capacity and uterine health
(rhodiola and astragalus)
• Counteracts hypertrophy and atrophy of the thyroid and
adrenal glands
Eleutherococcus Senticosus
Academic Press: London, UK, 1985; Volume 1, pp.156–209.

22. • 3-10 mls/day 1:3 liquid extract daily
• 10-15 mls 1:5 tincture daily
• 1-4 gr/day dry root
• Standardized preparations of Eleutheroside E
• 2 gr/day reduces frequency of recurrent herpes simplex outbreaks*
• Combines well with Rhodiola and Schisandra
Eleutherococcus Dosage
Williams M, Immunoprotection against herpes simplex II by Eletherococcus root extract, J Alt
Comp Med 13 (1995);9-12

23. 23
Reishi
Active constituents:
• Polysaccharides
• Immunomodulating proteins
• Steroidal saponin glycosides
Influences:
• Adrenal-hypothalamic-pituitary axis
• Regulates inflammation
• Circadian rhythm
• Sleep cycles
• Reduces stress

24. • Anti-fatigue - 200 mg three times a day
• Insomnia – 600 mg dose**
• Mild – Moderate Depression-170 mg or 340 mg twice daily)/placebo
for 6 weeks*
• 4-8 ml/d liquid extract
• 200-600 mg/d dried root
• 100 mg of extract standardized to 3 percent rosavins and 0.8-1 percent
salidroside, as the naturally occurring ratio of these compounds is approximately
3:1.
• A high dose-daily intakes of 1,000 mg
Rhodiola Dosage
*Nord. J. Psychiatry 2007, 61, 2343–2348
**Pharmaceuticals 2010, 3,188-224; doi:10.3390/ph3010188

25. • Rhaponticum carthamoides
• Common name: Leuzea or Maral Root, derived
from the fact that the Maral deer fed on this plant.
• Part Used: Root
• Herbaceous plant native to the sub-alpine and
alpine meadows of Siberia.
• Traditionally used as an energizing or tonic remedy
after long Siberian winters
• This plant was often combined with Rhodiola rosea
in traditional Siberian folk medicine and is still used
by modern Russian athletes.
Rhaponticum

26. • Active Constituents:
• Levseins (over 10 different ecdysterones), which increase activity of the cellular
compartments where protein synthesis takes place, thus enhancing muscle protein synthesis
• 25 years of research and clinical study has gained this plant entry to the Official
Russian Pharmacopoeia.
• Recommended for: increasing work efficiency, athletic performance and recovery
after muscular workloads. Stimulates muscle growth by increasing protein
synthesis in the muscle.
• A synthetic version was manufactured in Russia and the US,
but the Rhaponticum extract proved superior to synthetic
versions.
Rhaponticum
26

27. How does Rhaponticum affect the physiology?
• Promotes anabolic metabolism, preserves mitochondria
• Increases working capacity of skeletal muscle and their content of glycogen
for fuel and increases ATP
• Increases glycogen to the brain, liver and muscles; has mental and physical
anti-fatigue effects
• Increases oxidative enzyme systems, decreases lipid peroxidation acting as
a free-radical scavenger
• Enhances protein synthesis in muscle tissue, builds lean muscle mass
• Increases muscle recovery, supports structural integrity of muscle
• Decreases fat deposition
• Restoration of lowered IgG, IgA and C3 concentrations, improving humoral
immunity
Rhaponticum
27

28. • Root, leguminosae
• Clears heat, moistens membranes
• Adrenal restorative
• Anti-inflammatory
• Mucoprotective, reduces irritation of the body’s
mucus membranes
• Can raise the blood pressure if pre-hypertensive
• 5-10 mls/day 1:5 liquid extract
• 1-4 g/day dry root
Licorice - Glycyrhiza glabra

29. • Licorice root helps decrease the breakdown
of cortisol thereby effectively increasing
cortisol levels.
• If cortisol levels are very low, a patient may
benefit from licorice root supplementation
at the appropriate times of the day.
• Adaptogens to support anabolic
metabolism
Support the Cortisol Cycle

30. • Scientific names: Cordyceps sinensis & militaris
• Aka Caterpillar mushroom
• In nature, this parasitic fungus grows on the caterpillar larvae of a
moth.
• Grows in the highlands (10,000 feet) of China, Tibet and Nepal
• Recently, cultivated varieties (Cordyceps militaris) have been
developed. These Cordyceps fruiting bodies are cultivated on
nutritious barley substrate.
• Research has shown that C. militaris and C. sinensis provide
similar support, and they are used interchangeably in TCM and
other branches of herbalism.
Cordyceps
30

31. Action
• Anti-inflammatory, antioxidant, anti-tumor, adaptogen,
immunomodulatory, endocrine modulator, hypolipidemic, tonic
• Promotes restoration and regeneration
• Decreases fatigue and increases physical endurance, vigor, and energy
• Enhances athletic performance and training
• Builds vitality when recovering from stress
• Oxygen free-radical scavenger
• Regulates testosterone and cortisol
• Supports liver function and acts to protect the liver from stressors, aids regeneration
• Immune regulating, building, and supporting to normal cell growth and development
• Safety: Research on this mushroom shows complete safety when consumed in recommended doses
Cordyceps
31

32. Restoration Happens at Night

33. Effecting the neuroendocrine system
• Thyroid modulating
• Supports blood sugar metabolism
• Enhances conception, fertility issues
• Regulates HPA axis
• Neuro-protective effects
• Promoter of learning and memory retrieval; cognitive enhancer
• Tonic- debility, chronic exhaustion, low WBC, increases hemoglobin*,
convalescence
Withania somnifera (Ashwagandha)
*Bone K, Clinical Application of Ayurvedic and Chinese Herbs, Warwick, Qld; Phytotherapy Press, 1996 p 137-41

34. • Somnifera means “sleepmaking”
• A randomized, double blind, placebo-controlled study to evaluate the
effects of ashwagandha (Withania somnifera) extract on sleep quality
in healthy adults.
• Deshpande, A., Irani, N., Balkrishnan, R., & Benny, I. R. (2020).
Ashwagandha - Withania somnifera
Sleep Medicine, 2020, 72, 28-36.

35. • 3-6 grams daily of the dried root
• 6-15 ml of a 1:2 fluid extract per day
• 300-500 mg of an extract standardized to contain 1.5 percent
withanolides
• 125 mg-250 mg/d WSE- CVS/ Glucose regulation*
• 125 mg-500 mg/d WSE for stress reducing effects*
• Generally safe, large doses have been shown to cause gastrointestinal
upset, diarrhea, and vomiting.
Dosage for Withania
*Biswajit Auddy, PhD1 et al; JANA Vol.11,No.1, 2008

36. • Anxiety and adrenals
• Overweight premenopausal women
• A decrease in transitory anxiety, although salivary
cortisol levels were not significantly reduced
• Magnolia has been demonstrated to improve
mood, increase relaxation, induce a restful sleep
and enhance stress reduction.
Magnolia (Magnolia officinalis)
Nutrition Journal 2008;7:11:1-6.
J Pharm Pharmacol 1998;50:819-826.

37. • Cortisol and Mood
http://www.ncbi.nlm.nih.gov/pubmed/23924268
• Anti-inflammatory Suppresses NF-kB
http://www.ncbi.nlm.nih.gov/pubmed/24893579
• Honokiol, a Multifunctional Antiangiogenic and Antitumor Agent
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842137/
• Enhanced GABAergic Neurotransmission in Hippocampal Neurons
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652012/
Magnolia References

38. • Refers to total neolignans (usually magnolol plus honokiol), which are
usually at 1-10% of a basic bark extract
• Dose: 160 mg to 500 mg depending on weight/condition of patient
• Caution: Avoid in pregnancy due to possible oxytocic effects
Magnolia

39. • Scientific name: Tree of Happiness
• “Calms the spirit”
• “Relieves constrained emotions”
• Parts used: Bark and flower
• Has an acrid taste
• Actions: Anxiolytic, anti-microbial, antioxidant, antiinflammatory,
anti-asthma, nervine, hepatoprotective and lipid-lowering
• Dosing: 3-5 mls 1:5 tincture, 3-5 grams dry herb TID
Mimosa Albizia julibrissin
39

40. • Nervine with immune-regulating and cancer-inhibiting effects.
• 5-HT receptor binding – depression, anxiety, irritability
• Neurotransmitter mechanisms via GABA, dopamine and serotonin
• Bioactive Compounds:
• High in saponins in many forms: triterpenes, monoterpenes, flavone saponins, alkaloids and
flavonoids
• Flowers high in Quercetin and Isoquercetin
• Supports:
• Person with low blood pressure, low mood, low thyroid, anxiety and poor energy
• Parasympathetic-dominant person
• Low thyroid function with female hormonal aggravation and low mood
• Linking endocrine system to the nervous system via the pituitary gland
• Decreases sleep latency
• Poor memory, mind chatter
Mimosa Bark
40

41. • Assists the HPA Axis deal with and adapt to everyday stressors;
foundational, supports adrenal function;
• Ashwagandha, Eleuthero, Holy Basil, Reishi
• Deep support of the HPA Axis for those in state of adrenal
fatigue/exhaustion
• Cordyceps, Licorice, Rhaponticum, Rhodiola
• Restores HPA Axis function at night, promoting a healthy sleep cycle,
repair, growth and restoration
• Ashwagandha, Magnolia, Mimosa
Adaptogen Wrap Up

42. • Never seems to get enough sleep, wakes up
tired but able to get up and going
• Always has a low time midafternoon looking
for a sweet or caffeine to boost their energy
• Notes that they feel tired soon after they
evening meal or may even fall asleep for a
short time while putting the kids to bed
• Gets a second wind and may stay up to 1-2
am
• Struggles with weight issues even though
they exercises regularly
Night Owl

43. • This person has had life challenging
situations for several years.
• Examples of this could be graduate
student, very stressful job, several
pregnancies with breastfeeding, periods
close together, PTSD, chronic fatigue
issues, super athlete for several years
coupled with acute injury to body over
that time and a very busy life.
Adrenal Burnout

44. Questions and considerations when
selecting herbal products

45. 5 Elements of Botanical Quality
1. Design: Evidence-based formulation & appropriate
dosage form
2. Authenticity: Ingredient identity is always verified
using validation
3. Potency: Ingredient & finished product potency
verified w/validated methods
4. Purity: No contaminants
5. Validation: Safety/ efficacy
✓ Efficacy
✓ Quality & Trust
✓ Transparency

46. Botanical Support for the HPA Axis*
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