Honokiol

Overall Health Benefits of Honokiol

• Wards off depression [1-8]
• Fights anxiety [9-13]
• Improves dental health [14-18]
• Reduces blood sugar levels [19-25]
• Promotes weight loss [26-27]
• Relieves pain [28-30]
• Fights cancer [31-64]
• Improves cognitive health [65-84]
• Improves sleep quality [85-87]
• Improves blood pressure [48, 88]

What is Honokiol?

Honokiol is one of the chemicals found in Magnolia bark that is believed to be up to 1000 times more potent than vitamin E with regard to its antioxidant properties. Since 100 A.D., Magnolia bark is used by ancient Chinese in the treatment of a plethora of medical conditions including gastrointestinal disorders, respiratory infections, and body pains. Recent research found that honokiol is mainly responsible for the diverse health benefits of Magnolia bark.

How Honokiol Works

Honokiol exerts its antioxidant properties by blocking reactive oxygen species (ROS), which are unstable molecules that can cause cellular damage and cell death. This effect can help protect against various types of diseases related to free radicals.

Chemical Structure of Honokiol

Research on Honokiol

A. Wards Off Depression

Honokiol can stimulate the production of brain chemicals called neurotransmitters, which has an effect on mood stabilization. This produces a relaxing and calming effect that can help fight symptoms of depression. Numerous studies support this potent antidepressant effect of honokiol:

1. In mice, administration of honokiol for 1-2 weeks resulted in reduced depressive-like symptoms and improved the levels of serotonin and noradrenaline – both of these brain chemicals are the main ingredients in antidepressant drugs. [1]
2. In stressed rodents, honokiol administration at 20 and 40 mg/kg significantly reduced chronic mild stress. [2-5]
3. In a mouse model of depression, honokiol administration exerted an antidepressant effect as evidenced by an improvement in mice behavior in a series of tests assessing depression. [6]
4. When combined with magnolol (another chemical in Magnolia bark) and ginger oil, honokiol produced synergistic antidepressant-like effects. [7-8]

B. Fights Anxiety

Aside from its antidepressant effects, honokiol has also been shown to fight anxiety by affecting the levels of certain brain chemicals:

1. Studies show that honokiol has the ability to reduce anxiety with fewer side effects than diazepam, an anti-anxiety drug. [9]
2. Studies also show that honokiol exerts its anti-anxiety effect by increasing the levels of gamma butyric acid (GABA). [10-13]

C. Improves Dental Health

Evidence suggests that honokiol can help fight tooth decay and oral infection:

1. A cell study showed that honokiol has potent antimicrobial activity against the bacteria Streptococcus mutans, which is responsible for plaque build-up. [14-15]
2. In human gingival cells, honokiol appears to exert antibacterial properties against a variety of bacteria that cause periodontitis (gum infection). [16]
3. A 2019 study published in the Molecules Journal found that honokiol is effective against seven pathogenic fungi. [17]
4. A 2018 study published in the ACS Infectious Diseases found that honokiol inhibits the growth and reproduction of various oral bacteria. [18]

D. Reduces Blood Sugar Levels

There’s also strong scientific evidence supporting the potential benefits of honokiol in diabetics and those with chronic blood sugar elevation:

1. In rats with type 2 diabetes, honokiol increased sugar tolerance of cells and insulin levels – both of which led to normal blood sugar levels. [19]
2. In diabetic mice, honokiol was shown to normalize blood sugar levels by counteracting the peroxisome proliferator-activated receptor gamma (involved in fat formation). [20]
3. One study found that honokiol reduces blood sugar levels by improving insulin signaling pathways. [21]
4. One in-vitro study demonstrated that honokiol promotes effective usage of blood sugar in fat cells derived from both humans and mice. [22-23]
5. In mice with type 2 diabetes, supplementation with a diet rich in honokiol improved insulin resistance, blood sugar and lipid metabolism, and inflammation. [24]
6. In diabetic mice, oral treatment with 200 mg/kg honokiol for 8 weeks significantly reduced fasting blood sugar. [25]

E. Promotes Weight Loss

When it comes to improving body composition, studies show that honokiol could help achieve a healthier weight by improving different health parameters:

1. A 2014 study published in the Oxidative Medicine and Cellular Longevity found that honokiol supplementation protects against obesity and insulin resistance caused by a high-fat diet. [26]
2. In high-fat-fed mice, supplementation with a diet high in honokiol reduced body fat accumulation, insulin resistance, and adipose (fat tissue) inflammation. [27]

F. Relieves Pain

Honokiol is a natural remedy for pain. Its pain-relieving properties are backed by high-quality studies:

1. In a mouse model of inflammatory pain, honokiol alleviated formalin-induced inflammatory pain without motor and cognitive side effects. [28]
2. In mice injected with glutamate, a substance that causes inflammatory pain, oral supplementation with honokiol reduced pain sensitivity by decreasing the levels of the inflammatory molecules substance P and prostaglandin E2. [29]
3. A 2018 study published in the Frontiers in Pharmacology found that injection of honokiol in a mouse model of inflammatory pain produced significant pain-relieving effects through inhibition of inflammatory mediators. [30]

G. Fights Cancer

As a potent antioxidant, honokiol may help fight various types of cancer and even lower one’s risk of getting this debilitating disease. There’s an overwhelming body of clinical evidence supporting the anti-cancer properties of honokiol:

1. A 2013 study published in the Current Molecular Medicine reported that honokiol prevents the communication of cancer cells and the growth and multiplication of tumors by inhibiting the activity of the proteins Nf-kB and STAT3. [31]
2. In mice with lung cancer, honokiol treatment for 12 days reduced tumor volume by 78%. [32]
3. In cisplatin-resistant human ovarian cancer, administration of honokiol inhibited tumor growth by 84-88%. [33]
4. Exposure of human prostate cancer cells to honokiol resulted in programmed cell death. [34]
5. A cell study on human colorectal cancer cells found that honokiol treatment led to increased programmed cell death at different tumor sites, thereby preventing the growth and reproduction of tumors. [35]
6. In mice with gastric cancer and human gastric cancer cells, honokiol administration led to programmed cell death and decreased the production of key molecules involved in the growth and reproduction of tumors. [36]
7. A cell study involving human pancreatic cancer cells found that honokiol treatment led to programmed cell death and increased the effectiveness of the chemotherapeutic drug gemcitabine. [37]
8. In ovarian tumor cells, exposure to honokiol induced programmed cell death and inhibited the growth of new blood vessels. [38]
9. In mice, skin application of honokiol prevented ultraviolet B-induced skin cancer development. [39]
10. In human breast cancer cells, treatment with honokiol inhibited the activity of cancer cell growth through induction of cell cycle arrest and programmed cell death. [40]
11. In human squamous lung cancer cells, honokiol treatment induced programmed cell death. [41]
12. Studies show that honokiol exerts its anti-cancer properties by inhibiting the protein nuclear factor kappa B (NF-κB), which is associated with cancer cell survival. [42-44]
13. In mice with lung cancer, administration of honokiol increased the efficacy of the chemotherapeutic drug cisplatin in suppressing tumor growth. [45-46]
14. In breast cancer models, honokiol treatment also increased the efficacy of the chemotherapeutic drug adriamycin in suppressing the progression of the tumor. [47]
15. A cell study also found that honokiol inhibits breast cancer cell migration by targeting nitric oxide and cyclooxygenase-2. [48]
16. A cell study assessing the effects of honokiol on breast cancer cells found that the treatment suppresses the growth of malignant cells via programmed cell death and cell cycle arrest. [49]
17. In mice with prostate cancer, honokiol administration inhibited the growth of cancer cells and reduced the levels of the prostate cancer marker prostate-specific antigen (PSA). [50]
18. In a human colorectal cancer cell line, honokiol induced programmed cell death in a dose-dependent manner. [51]
19. In human gastric cancer cells, treatment with honokiol reduced tumor size by causing programmed cell death. [52]
20. In a rat model of brain cancer, honokiol injection given twice per week for 3 weeks significantly reduced tumor volume. [53]
21. A cell study also demonstrated the inhibitory effects of honokiol on the growth and proliferation of oral cancer cells. [54]
22. In head and neck squamous cell carcinoma (HNSCC), honokiol induced programmed cell death of cancer cells at doses of 3.3 to 7.4 micromol/L. [55]
23. Studies have also shown that honokiol is effective against various leukemia cell lines. [56-58]
24. Honokiol treatment of tumor cells collected from patients with multiple myeloma enhanced cell cytotoxicity and programmed cell death induced by the anti-cancer drug bortezomib. [59]
25. When administered along with the chemotherapeutic drug doxorubicin, honokiol increased the drug efficacy. [60-61]
26. In human chondrosarcoma cells (bone cancer involving cartilage cells), administration of honokiol reduced tumor volume by 53%. [62]
27. In human fibrosarcoma cells (cancer of the connective tissue), honokiol inhibited the migration of cancer cells. [63]
28. In human liver cancer cells, honokiol administration significantly reduced the growth and multiplication of malignant cells. [64]

H. Improves Cognitive Health

Studies show that honokiol also has cognitive-boosting effects that may be beneficial in age-related cognitive dysfunction and medical conditions that cause cognitive impairments:

1. A 2013 study published in Frontiers in Neurology found that honokiol protects the central and peripheral nervous systems from various forms of nerve damage. [65]
2. Studies show that honokiol exerts its beneficial effects on nerve tissues of the brain by crossing the blood-brain barrier. [66-67]
3. In rats, honokiol administration improved performance on learning and memory tests and protected against brain damage caused by inadequate blood flow. [68-69]
4. Cell studies found that honokiol improves cognitive function by promoting healthy connections among nerve cells. [70-72]
5. In mice, honokiol administration preserved enzymatic mitochondrial function in the brain by protecting against oxidative stress. [73]
6. Honokiol also suppressed nerve damage induced by a stroke in mice. [74]
7. In rats, honokiol protected against brain injury induced by a low blood supply. [75-76]
8. One study found that honokiol inhibits the inflammatory reaction during stroke, thus preventing further brain damage and cognitive dysfunction. [77]
9. Studies also show that honokiol may inhibit the repetitive firing of neurons by blocking glutamate, which helps restore communication between nerve cells of the brain. [78-79]
10. In aged rats, oral honokiol administration at 1 mg/kg prevented age-related memory and learning deficits. [80]
11. A cell study found that honokiol protects against Alzheimer’s disease by significantly decreasing β-amyloid (Aβ)-induced nerve cell death in the brain. [81]
12. In a mouse model of Alzheimer’s disease, administration of a honokiol-containing extract of Magnolia officinalis prevented lipopolysaccharide (LPS)-induced memory deficiency by reducing inflammation and β-amyloid levels. [82-83]
13. In mice with scopolamine-induced learning and memory deficits, honokiol administration significantly reduced related cognitive impairments. [84]

I. Improves Sleep Quality

Researchers also suggest that honokiol may help fight insomnia and other sleeping problems by affecting the stages of sleep:

1. In mice, honokiol administration promoted non-rapid eye movement (dreamless sleep) episodes by increasing the production of GABA in the brain. [85-86]
2. In menopausal women, administration of magnolia extract containing honokiol improved sleeping patterns. [87]

J. Improves Blood Pressure

Evidence also suggests that honokiol possesses mechanisms similar to that of blood pressure-lowering medications:

1. A study found that honokiol has the ability to regulate blood pressure by controlling the levels of nitric oxide, a substance that widens blood vessels. [48]
2. In hypertensive rats, honokiol reduced blood pressure by causing the blood vessels to dilate or widen. [88]

Associated Side Effects of Honokiol

Honokiol side effects are very uncommon. There have been some side effects associated with its use wherein the patient had one of the issues listed below at some point while being on honokiol. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of honokiol. Despite this, it was listed as a side effect associated with honokiol even though these associated side effects are very uncommon.

Side effects associated with honokiol may include the following:

• Diarrhea
• Drowsiness
• Dry mouth
• Gas
• Headaches
• Insomnia
• Sleepiness

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