Magnolia Officinalis (commonly called Houpu Magnolia or Magnolia bark) is a specie of Magnolia native to the mountains and valleys of China at altitudes of 300-1500 m.
It is a deciduous tree growing to 20m in height. The bark is thick and brown but does not fissure. The leaves are broad, ovate, 20-40 cm long and 11-20 cm broad. The flowers are fragrant, 10-15 cm wide, with 9-12 (rarely to 17) white tepals, and appear from May to June.
The bark of Magnolia Officinalis is dried in the shade at room temperature and stored in a dark, cold room until use. The air-dried bark of Magnolia officinalis is cut into pieces and extracted twice with 95% ethanol (four times as much as the weight of the dried plants) for 3 days at room temperature.
After filtration, the filtrate is re-filtered through filter paper and concentrated under reduced pressure. The extract is then suspended in distilled water.
The ethanol extract of Magnolia Officinalis contained 16,6,% 4-O-methylhonokiol followed by 16,5% honokiol, 12,9% magnolol and 42-45% others.
Compounds
Honokiol is a lignan isolated from the bark, seed cones, and leaves of trees belonging to the genus Magnolia. It’s the most widely researched active constituent of the bark.
Honokiol has been extracted from a number of species of Magnolia native to many regions of the globe. The compound itself has a spicy odor. It’s an isomer of magnolol.
Because of its physical properties, honokiol can readily cross the blood brain barrier and the blood-cerebrospinal fluid barrier. As a result, honokiol is a potentially potent therapy with high bioavailability.
Magnolol, the other compound of Magnolia bark, is a lignan as well. The compound exists at the level of a few percent in the bark of species of magnolia, the extracts of which have been used in traditional Chinese and Japanese medicine.
4-O-Methylhonokiol is a neolignan, a type of phenolic compounds.
Medical uses
Honokiol has a wide range of biological and clinically relevant effects, without appreciable toxicity.
It is a pleiotropic compound, meaning it is able to act on the body through a number of pathways. This diversity of interaction makes it a viable therapy for a number of conditions in the cns, cardiovascular system, and gastrointestinal system. It can alleviate gastric and abdominal distension and other digestive discomforts, reduce the symptom of cough and asthma due to the aecumulation of phlegm in the lung, and treat syndromes caused by emotional distress. It has been shown to have antitumorigenic, anti-inflammatory, and antioxidant effects as well.
Honokiol induced apoptosis
In non-small cell lung cancer, honokiol suppressed cancer cell growth and induced apoptosis through influence on multiple cell-signaling pathways
In the treatment of leukemia, honokiol induced cell cycle arrest and apoptosis through the inhibition of specific cancer cell survival signals ( The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells, 2005).
A 2012 study showed honokiol’s ability to stop the proliferation and spread of malignant melanoma. In this study, honokiol induced cancer cell death and blocked proliferation by regulating cell cycle arrest through multiple signaling pathways (Honokiol induces cytotoxic and cytostatic effects in malignant melanoma cancer cells, 2012).
In vitro research suggests that honokiol crosses the BBB and may reach therapeutic concentrations in the brain via passage through the tight junctions formed by cerebral endothelial cells (CECs). Honokiol reached brain tissues following intravenous injection in rodents (25 mg/kg). Ultimately, this study demonstrated that honokiol was able to induce apoptotic insults to neuroblastoma cells through a Bax-mitochondrion-cytochrome c-caspase protease pathway, at concentrations that traversed the BBB (Honokiol traverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax-mitochondrion-cytochrome c-caspase protease pathway, 2012)
Honokiol acts in many other types of cancer
NF-κB and STAT3 are two ubiquitously expressed transcription factors controlling the expression of a wide array of genes involved in numerous physiological processes including development, differentiation, immunity, metabolism and cancer. Aberrant activation of these transcription factors is common in many malignancies, and is pathologically significant in early and late developmental steps of cancer. Honokiol has been shown to inhibit NF-κB activation through suppression of Akt ( a citosolic proteinvwhose activity consists in the phosphorylation of various protein substrates in serine and threonine residues, often leading to their inactivation. The activation of Akt causes as a result of the effective activation of biochemical pathways that lead to cell growth and resistance to apoptosis) and activation of IKK (inhibitor kinase), which then leads to phosphorylation and subsequent IκBα degradation. IκBα keeps NF-κB sequestered in the cytoplasm in an inactive state and its degradation leads to nuclear translocation of NF-κB and transcriptional activation. STAT3, among various STAT proteins, is constitutively activated in many human cancer cells and can be inhibited by honokiol. Honokiol suppresses STAT3 activity induced by IL-6, one of the many growth factors that activate STAT3.
Other role of honokiol was associated with downregulation of EGFR (epidermal growth factor receptor) signaling in human breast cancer cells . Honokiol has been shown to downregulate the expression and phosphorylation of both c-Src and EGFR, causing reduced activation of downstream signaling molecules. Honokiol also inhibited EGFR signaling in head and neck squamous cell carcinoma cells (HNSCC). Furthermore, honokiol also promoted the growth inhibitory activity of the EGFR-inhibiting agents erlotinib and lapatinib in HNSCC and Her-2 over-expressing breast cancer cells, respectively. There are clear evidence for the suppressive effects of honokiol on EGFR and its downstream signaling in cancer cells.
The receptor EGFR binds a protein, EGF (or TNFalpha), and this binding activating EGFR that mates with another receptor EGFR. This mechanism leads rapprochement of cytoplasmic domains that possess a tyrosine kinase activity able to phosphorylate and activate other proteins, such as RAS, which is able to activate MAP KINASE which quickly lead to differentiation and cell proliferation. EGFR not only activates the RAS, but also the PI3K pathway, whose main target is AKT that following activation inhibits apoptosis.
Honokiol inhibiting EGFR going to suppress uncontrolled cell growth.
Honokiol Suppresses Renal Cancer Cells’ Metastasis
Honokiol Suppresses Renal Cancer Cells' Metastasis Via Dual-Blocking Epithelial-Mesenchymal Transition and Cancer Stem Cell Properties through Modulating miR-141/ZEB2 Signaling. Honokiol inhibited tumor growth in vivo. It was found that honokiol could up-regulate miR-141, which targeted ZEB2 and modulated ZEB2 expression. Honokiol reversed EMT and suppressed CSC properties partly through the miR-141/ZEB2 axis.
MiR-141 is a putative tumor-suppressive miRNAs which is downregulated in RCC ,honokiol can upregulate the expression level of miR-141. It may be possible that honokiol elevates miR-141 expression through inhibiting histone deacetylases which are suggested to be responsible for the downregulation of miR-141.
ZEB2, a target of miR-141, is a master factor involved in EMT and CSC and is frequently overexpressed in RCC.
Honokiol exerted anti-tumor activities through modulating the miR-141/ZEB2 axis, and that ectopic overexpression of ZEB2 could rescue the effect of honokiol on EMT and CSC properties.
Honokiol may be a suitable therapeutic strategy for RCC treatment.
