Honokiol: General presentation

What is Honokiol?

honokiolHonokiol is an active molecule that is extracted from the various organs of the Magnolia plant, including bark, buds and seed cones. It is a phytonutrient that has a long history of use in phytotherapy due to its neuroprotective properties.

Honokiol is a polyphenolic compound that belongs to a class of neolignan biphenols. The chemical formula is C18H18O2, and the molar mass is 266, or 266334 g / mol.

Honokiol is used in traditional Asian medicine along with other molecules such as magnolol, obovatol and 4-O-methylhonokiol.

Sources of Honokiol

The various species of Magnolia contain different levels of honokiol. The best sources of honokiol are the genus Magnolia grandiflora, which is native to South America, and the genus Magnolia dealbata, a species of Magnolia that originated in Mexico (1). A number of other Magnolia species have also been used in traditional herbal medicine, including Magnolia obovata, Magnolia officinalis and Magnolia biondii, though the popularity of these herbs has decreased in recent years (2).

Magnolia grandiflora, the best source of honokiol
Magnolia grandiflora, the best source of honokiol

A variety of methods have been employed to extract and isolate the honokiol compound. It should be noted that the honokiol compound has a chemical structure that is similar to its isomer, magnolol. In fact, the position of the hydroxyl group within the honokiol compound is the only real difference. This is why the two molecules exhibit highly similar actions and medicinal properties. The striking similarity between the two compounds has played a role in the development of techniques to extract the active molecule. The method used to isolate the honokiol compound was initially restricted to either electromigration or HPLC (high performance liquid chromatography), which uses a preparatory or analytical separation of molecules.

Fortunately, modern extraction techniques have made it possible for supplement manufacturers to obtain a purer form of honokiol. The laboratory L. Arbiser extraction technique, which was discovered in 2006, generates magnolol acetonide at the phenol hydroxyl groups of magnolol using gas chromatography, or GC. This method allows technicians to quickly isolate the honokiol molecules.

Chromatography Journal published the results of a study in 2007 that demonstrated a new high-speed extraction method that relies on High-capacity Countercurrent Chromatography (HSCCC) to obtain honokiol with a purity of 98% in just one hour (3).

Standardized Honokiol Extract

The best way to take advantage of honokiol is to use a standardized extract with a purity greater than 90%. Quality standardized Magnolia extracts are manufactured in accordance with rigorous quality controls and laboratory analysis. There is little doubt that a standardized extract is far superior to powdered supplements that contain the pulverized leaves and bark of the Magnolia plant.

Reputable dietary supplement manufacturers clearly describe the method that was employed to isolate and purify their Magnolia extract product. An honokiol extract can be offered in a pure form that contains no additives, or in the form of a compound that includes other active ingredients. Positive synergy can often be obtained by adding ingredients such as magnesium to boost the antistress effect of the supplement. Honokiol is a white powder that is easy to identify because of its unique scent, which has been compared to natural anesthetics such as propofol, lidocaine and etomidate.

Another important biological property of the honokiol compound is its ability to interact with blood plasma proteins. The albumin protein, for example, has a high proportion of Plasma concentrates and nearly 300 different proteins. The large concentration of albumin in circulating blood plasma ensures the transport of medicinal molecules and other active supplement ingredients. Researchers have noted that the pharmacokinetic interaction between polyphenols such as honokiol and albumin is quite interesting.

It turns out that the interaction between polyphenols and proteins such as albumin ultimately influences the absorption, distribution, metabolism and excretion of the principle active ingredient and its metabolites. The relationship between blood plasma proteins and active ingredients also influences the pharmacodynamic effect of the principle active ingredient on organisms (4).

Numerous research studies have concluded that honokiol exhibits remarkable antioxidant properties. Researchers consider honokiol to be one of the most powerful antioxidants ever discovered. Dr. Isaac Eliaz, researcher, licensed acupuncturist and pioneer of holistic medicine, is founder of the Medical Clinic Amitabha in Santa Rosa, California. According to Dr. Eliaz, honokiol is 1,000 times more powerful and effective than Vitamin E.

Uses of Honokiol

The use of honokiol to treat various diseases in Asian countries such as China, Japan and Korea goes back many centuries. Long before the honokiol molecule was isolated and manufactured as a dietary supplement, the Asian people made decoctions and herbal teas from dried Magnolia bark to calm anxiety, promote sleep, treat nervous disorders and induce analgesic effects (5). In traditional Chinese medicine, Magnolia is used to stimulate and circulate the vital energy of the body, known as “Qi,” and promote the burning of fat mass in people suffering from obesity. China is currently among the largest producers of Magnolia bark in the world, producing nearly 200 tons annually. Government officials hope to increase production levels to 1,500 tons per year.

Magnolia, in the form of a standardized extract, dried powder or mother tincture, is included in the pharmacopoeia of the People’s Republic of China. Moreover, Magnolia is included in many drug formulations intended to treat anxiety. Asian scientists have recognized the synergistic action between honokiol and magnolol, the two primary active components of Magnolia. Honokiol is known to induce an antianxiety effect and magnolol is considered to be an antidepressant (6).

Honokiol has been the subject of numerous scientific experiments for more than 20 years and is currently one of the treatments recommended by phytotherapists and nutritionists to treat various health problems. Scientists have recognized the beneficial effects of honokiol on the central nervous system and its ability to cross the blood-brain barrier. One experiment revealed that the honokiol molecule could easily reach the neuronal tissues and act directly as a protective agent against neuronal degradation. Scientists have also discovered anti-tumor properties in some experimental subjects (7) (8). Honokiol significantly reduced the effects of stroke and improved the memory when administered intravenously to rodents at a dose of 10-4 mg / kg and 10-3 mg / kg (9).

Honokiol is also considered to be an anxiolytic par excellence and is, therefore, often recommended for the medical treatment of anxiety, psychomotor agitation, spasms, insomnia and alcohol withdrawal syndrome. The medicinal effect of honokiol in alcohol withdrawal syndrome is similar to Benzodiazepines like Diazepam. The honokiol molecule can also interact with GABA A receptors (GABA A), which are ion channels of the membranes of neurons and the main targets of pharmacological molecules with anxiolytic, sedative, hypnotic and anesthetic effects. Researchers observed this action among rats that received regular doses of 0.2 mg / kg of honokiol. It was also shown that the effect induced by the administration of honokiol could be halted by administering Flumazenil subcutaneously. Flumazenil happens to be a GABA A channel antagonist (10).

In another experiment comparing the efficacy of honokiol with that of Diazepam, it was determined that a group of nervous and timorous rats experienced a significant improvement when a small dose of honokiol was administered for 7 consecutive days. The rodents became quieter, relaxed and vigorous. The experiment also revealed that the rodents became more curious when placed in a labyrinth after being treated with honokiol. The Diazepam group did not exhibit a similar positive outcome. Researchers noted that the rodents became dependent on the dose of Diazepam, and that their condition even deteriorated when the dose was reduced (11).

Another peculiarity of honokiol administration observed by scientists is its ability to modulate the activity of certain neurotransmitters in the brain, including acetylcholine, or ACh. The ACH neurotransmitter plays an important role in the central nervous system, including learning and memory. Research has clearly shown that honokiol is able to stimulate the release of acetylcholine and inhibit the action of acetylcholinesterase. Improvement of cholinergic function is regarded as essential in the fight against Alzheimer’s disease. A significant deficiency of acetylcholine and acetyltransferase choline has been observed in subjects diagnosed with Alzheimer’s disease (12).

Honokiol Research

Modern research focusing on the bioactive properties of honokiol has confirmed the numerous benefits of standardized Magnolia extract. Experiments conducted by scientists have focused on the antioxidant action of honokiol. Various observations have revealed the protective role of the honokiol molecule vis-a-vis the mitochondria in the cells of the brain, liver and heart. Honokiol protects these vital organs from the harmful effects of free radicals. In its role as a powerful antioxidant, honokiol has a unique capacity to prevent the peroxidation of lipids, a primary risk factor for cardiovascular disease. (13).

Honokiol also helps in the treatment of liver and colon cancer. Scientists have found that this polyphenol has the power to inhibit or even totally halt the growth and proliferation of cancer cells (14). Additional research studies have concluded that honokiol exhibits beneficial properties in the treatment of leukemia (15). A study of people with chronic lymphocytic leukemia(CLL) and type B lymphocyte proliferation cells were sensitive to the cytotoxic effects of honokiol when the leukemia cells were incubated in a substance containing honokiol for a period of 6 to 24 hours.

The antiviral effect of the honokiol molecule has also attracted the attention of scientists. In vitro experiments have shown that honokiol can inhibit the progress of the hepatitis C virus in addition to protecting liver cells from the consequences of infection. The most dangerous form of infection in hepatitis C patients is the chronic form of cirrhosis (16).

Finally, another important virtue of honokiol is its ability to normalize blood glucose levels. It has been convincingly shown that the honokiol molecule can reduce blood sugar levels and prevent weight gain in diabetic mice. This is due to its agonist action vis-à-vis the gamma PPAR
(peroxisome proliferator-activated receptor), which are proteins of the nuclear receptor group, liaison, lipids and transcription of target genes involved in adipogenesis and metabolism. As an agonist, honokiol mimics the action of these PPAR and has a similar physiological action that can limit the production of adipose tissue and fat accumulation in adipocytes (17).

How To Take Honokiol?

The use of an extract of Magnolia as a complement to food should not cause any health related side effects if the prescribed doses and treatment instructions are strictly observed. The recommended daily dose is between 30 and 90 mg per day. It is recommended that extract of Magnolia capsules be taken at mealtime, but are not intended to replace a healthy and balanced diet.

Certain individuals, especially young children, pregnant and breastfeeding women, patients using medication or supplements with serotonergic activity, antidepressant, anti-nausea, and medications intended for treatment of pain or migraine headaches are advised to consult a licensed physician prior to taking extract of Magnolia. Although honokiol may be perfectly safe to take with pain medication, antidepressants and anxiolytics, caution is advised in order to avoid the possibility that an overdose could induce serotonin syndrome. This condition can result in an excess of serotonin in the central and peripheral nervous system, accompanied by gastrointestinal symptoms such as diarrhea and nausea, neuropsychiatric signs such as hallucination, agitation, tremors, muscle stiffness, symptoms of nervousness, hyperthermia, high blood pressure or tachycardia.

If you experience symptoms of weakness, abdominal pain, dizziness or skin irritation while taking extract of Magnolia, stop administering all nutritional supplements and speak with a physician. In principle, standardized extracts are safer than powdered Magnolia products. Consuming the bark of Magnolia or its buds in the form of an infusion or decoction, especially in large quantities, is known to cause the previously mentioned side effects.

Purchasing a standardized Magnolia extract with a purity rating of more than 90% is the best way to maximize the benefits of honokiol while eliminating undesirable side effects. Quality nutritional supplements are subjected to laboratory analysis and strict quality control standards. There is no substitute for quality when it comes to purchasing an herbal supplement. Always purchase your herbal supplements from a highly rated vendor that thoroughly researches every product that they recommend to customers.

 

References 

(1) Woodbury, Anna; Yu, Shan Ping; Wei, Ling; García, Paul (2013). « Neuro-Modulating Effects of Honokiol: A Review ». Frontiers in Neurology.4(7): 4111–5.
(2) Lee, Young-Jung; Lee, Yoot Mo; Lee, Chong-Kil; Jung, Jae Kyung; Han, Sang Bae; Hong, Jin Tae (2011). « Therapeutic applications of compounds in the Magnolia family ». Pharmacology &Therapeutics.130(2): 157–76.
(3) Chen, Lijuan; Zhang, Qiang; Yang, Guangli; Fan, Linyu; Tang, James; Garrard, Ian; Ignatova, Svetlana; Fisher, Derek; Sutherland, Ian A. (2007). « Rapid purification and scale-up of honokiol andmagnolol using high-capacity high-speed counter-current chromatography ». Journal of Chromatography A. 1142(2): 115–22.
(4) « Interactions of polyphenols with plasma proteins: insights from analytical techniques ». Review article Jaldappagari S, et al. Curr Drug Metab. 2013.
(5) Sarris, Jerome; McIntyre, Erica; Camfield, David A. (2013). « Plant-Based Medicines for Anxiety Disorders, Part 1 ». CNS Drugs. 27(3): 207–19.
(6) Nakazawa T. et al., Metabolites of orally administered magnolia officinalis extract in rats and man and its antidepressant-like effects in mice, J. Pharm. Pharmacol., 2003.
(7) Wang X, Duan X, Yang G, Zhang X, Deng L, Zheng H, et al.Honokiol crosses BBB and BCSFB, and inhibits brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model.
(8) Lin JW, Chen JT, Hong CY, Lin YL, Wang KT, Yao CJ, et al. Honokiol traverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax -mitochondrion-cytochrome c-caspase protease pathway. Neuro Oncol(2012)14(3):302–1410.1093.
(9) Liou KT, Lin SM, Huang SS, Chih CL, Tsai SK. Honokiol ameliorates cerebral infarction from ischemia-reperfusion injury in rats. Planta Med(2003)69(2):130–410.
(10) Ai J, Wang X, Nielsen M. Honokiol and magnolol selectively interact with GABAA receptor subtypes in vitro. Pharmacology (2001)63(1):34–4110.
(11) Kuribara H. et al., Behavioural pharmacological characteristics of honokiol, an anxiolytic agent present in extract of magnolia bark, evaluated by an elevated plus-maze test in mice, J. Pharm. Pharmcol., 1998 Jul, 50(7): 819-26.
(12) Hou Y.C. et al., Honokiol and magnolol increased hippocampal acetylcholine release in freely-moving rats, Em. J. Chin. Med., 2000, 28(3-4): 379-84.
(13) Lo Y.C. et al., Honokiol and magnolol isolated from magnolia officinalis protect rat heat mitochondria against lipid peroxidation, Biochem. Pharmacol., 1994 Feb, 9 ; 47(3) : 549-53.
(14) Saito J, Sakai Y, Nagase H. In vitro anti-mutagenic effect of magnolol against direct and indirect mutagens. Mutat Res. 2006 Oct 10;609(1):68-73. Epub 2006 Aug 1.
(15) Zhong WB, Wang CY,et al. Magnolol induces apoptosis in human leukemia cells via cytochrome c release and caspase activation. Anticancer Drugs. 2003 Mar;14(3):211-7.
(16) Lan, KH; Wang, Ying-Wen; Lee, Wei-Ping; Lan, Keng-Li; Tseng, Szu-Han;Hung, Li-Rong; Yen, Sang-Hue; Lin, Han-Chieh; Lee, Shou-Dong (2012). « Multiple effects of Honokiol on the life cycle of hepatitis C virus ». Liver International.32(6): 989–97.
(17) Atanasov, Atanas G.; Wang, Jian N.; Gu, Shi P.; Bu, Jing; Kramer, Matthias P.; Baumgartner, Lisa; Fakhrudin, Nanang; Ladurner, Angela; Malainer, Clemens; Vuorinen, Anna; Noha, Stefan M.; Schwaiger, Stefan; Rollinger, Judith M.; Schuster, Daniela; Stuppner, Hermann; Dirsch, Verena M.; Heiss, Elke H. (2013). « Honokiol: A non-adipogenic PPARγ agonist from nature ».Biochimica et Biophysica Acta (BBA) – General Subjects.1830(10): 4813–4819.