Herbs And Phytochemicals: International Study Explores The Phytochemical Honokiol From The Plant Magnolia Officinalis For Its Anticancer Properties

Herbs And Phytochemicals: Cancer, a leading cause of death worldwide, is characterized by uncontrolled cellular growth and has a multifactorial etiology involving genetics, environment, and lifestyle factors, and continues to claim towering mortality and morbidity. Contemporary anticancer therapy has proved beneficial during the early stages of cancer; however, it suffers limitations about the side-effects, poor patient compliance, and drug resistance. This has led to an inclination towards traditional herbal medicine; natural products have played a pivotal role in human health for millennia, not only as a source of nutrition but also as medicines.


 
Historically, many of the drugs available today have their roots in traditional remedies sourced from plants, animals, and microorganisms. Traditional herbal medicines have long been used to promote health benefits and disease treatment. A few examples include Japanese herbal medicines of Chinese origin, called ‘Kampo’ that exert beneficial effects over the side effects of cancer chemotherapy. Kampo therapy has been under investigation in animal models for its effect on chemotherapy-triggered side effects. Indian traditional medicine or ‘Ayurveda’ has also been known to detoxify the body from free radicals and toxins, which can be useful for cancer patients. Similarly, the traditional Chinese medicine ‘Houpu’ frequently uses Magnolia officinalis and Magnolia obovata, while the traditional prescriptions Hange-koboku and Sai-boku-to containing Magnolia bark are quite popular in clinical practice in Japan.
 
The Magnolia species consists of highly potent bioactive compounds, which include neolignan compounds, obovatol, magnolol, 4-O-methylhonokiol, and honokiol.
 
Plant-derived compounds have shown promising results in the prevention and treatment of various diseases, including cancer. The search for natural anticancer agents has been a cornerstone in the fight against different types of diseases, primarily due to the perceived reduced side effects and potential synergistic effects of natural compounds.
 
Honokiol, a biphenyl neolignane compound extracted from the bark of the magnolia tree (Magnolia officinalis and Magnolia grandiflora), is one such molecule that has garnered significant attention in recent years; this compound, along with its analogues, has shown notable anti-inflammatory, antioxidative, and anticancer properties in various in vitro and in vivo studies.
 
Lignans are a diverse group of polyphenolic compounds that are found primarily in plants, especially seeds, whole grains, and vegetables; over the years, extensive research has unveiled a plethora of pharmacological activities associated with lignans. They possess significant antioxidant properties which help counteract oxidative stress by neutralizing free radicals, this mechanism can potentially help prevent a range of diseases, including those of the cardiovascular system and cancer.

The dietary intake of lignans to a reduced risk of certain types of cancer, especially breast and prostate cancer, they are believed to influence tumor progression and metastasis.
 
Lignans, like enterolactone and enterodiol, have been shown to modulate hormone metabolism, which may partly explain their protective role against hormone-dependent cancers.
 
Lignans can have a ben eficial effect on heart health by improving lipid profiles, reducing blood pressure, decreasing the risk of atherosclerosis, reducing platelet aggregation, which can help prevent thrombotic events. Lignans have shown promising activity against a range of pathogens, including bacteria, viruses, and fungi, this makes them potential candidates for developing new antimicrobial agents.
 
By modulating various inflammatory pathways, lignans can potentially help in conditions like arthritis, asthma, and other inflammatory disorders.
 
Some Herbs And Phytochemicals studies suggest that lignans might have a role in improving bone health and preventing osteoporosis, potentially through their estrogenic activities. There's emerging evidence that lignans can offer protection against neurodegenerative diseases, such as Alzheimer's, this is possibly due to their antioxidant and anti-inflammatory properties.
 
Lignans may help in the management of diabetes by improving insulin sensitivity and reducing blood glucose levels and can exert hepatoprotective effects, potentially useful in conditions like fatty liver disease or hepatitis.
 
Some lignans are known to bind to estrogen receptors and can act as both estrogen agonists and antagonists; this dual activity can be beneficial in various conditions, like menopausal symptoms and hormone-dependent cancers.
 
The anticancer activity of Honokiol lies in its multifaceted mechanism of action against cancer, making it a potent candidate for cancer prevention and therapy. Honokiol is a small molecule polyphenolic compound belonging to the lignan family of phytochemicals that possesses a wide range of anticancer activities. Looking at the broad-spectrum anticancer properties of honokiol, it is apparent to develop analogues or perform a chemical modification on honokiol to obtain the desirable profile.
 
Bioavailability and Pharmacokinetics of Honokiol
The oral bioavailability of honokiol is of particular interest, given its traditional use in herbal medicine preparations. In preclinical studies, honokiol showed moderate to good oral bioavailability; this can be attributed to its lipophilicity, which facilitates its absorption across the gastrointestinal tract; its bioavailability can be compromised due to its metabolism in the liver. After oral administration, honokiol is rapidly absorbed into the bloodstream due to its lipophilic nature.
 
Honokiol as a Potential Anticancer Drug: Mechanistic Insights from Preclinical Studies
Honokiol's anticancer properties are diverse and mediated through several mechanisms; targeted signaling pathways by honokiol include STAT3, NF-kB, mTOR, EGFR, and caspases mediated common pathway that regulates the tumorigenesis and its metastasis.
 
Honokiol Analogues: Mechanistic Insights and Structure-Anticancer Activity Relationship
Honokiol is known to inhibit the key oncogenic pathways that synchronize to manifest cancer. The anticancer activity of honokiol can be tuned by synthesizing its analogues containing the basic honokiol skeleton appended with varied substituents. The electronic, positional, and functional effects of various substituents on the honokiol molecule have been appraised. Mainly, the hydroxyl group on B ring predominantly determines the bioactivity of honokiol analogues, with the possibility of improving bioavailability and efficacy.
 
Analogues with Improved Bioavailability
Honokiol dichloroacetate and fluorinated honokiol analogue bistrifluoromethyl-bis-(4-hydroxy-3-allylphenyl) methane (hexafluoro) display an improved lipophilicity over honokiol. These compounds demonstrate potent bioactivity against A375 melanoma but the analogues proved superior over the other compound. The treatment of tumor cells with these compounds results in the induction of respiratory enzyme succinate dehydrogenase B that indicates the onset of promising anticancer activity.
 
Contemporary Formulations for Drug Delivery Systems of Honokiol in Cancer Cells: Advantages and Therapeutic Perspectives
Honokiol has been shown to exhibit excellent anti-cancer properties, which makes it a potential candidate for targeted and sustained delivery to various cancer cell lines. The major challenge faced by conventional chemotherapy is the development of resistance that further aggravates the toxicity posed by enhancing the drug dose. One approach to targeted and sustained delivery of honokiol is with polymeric nanoparticles, liposomes, and dendrimers. These nanoparticles can be modified to improve bioavailability and target specific cancer cells while minimizing the damage to healthy tissues.
 
Limitations
Honokiol and its derivatives are bioactive compounds of interest in the field of chemotherapy due to the many remarkable effects they have had in various preclinical in vitro and in vivo experimental studies. However, numerous limitations restrict their use as first-line chemotherapeutic compounds due to the lack of translational studies that clearly establish the effective therapeutic dose in humans, the lack of clinical studies in humans, the lack of toxicological studies highlighting adverse effects, and potential drug interactions.
 
Overall Conclusion
The side effects of contemporary chemotherapy have raised the necessity for the development of physiologically benevolent molecules without compromising bioactivity. Honokiol has been a part of traditional medicine for decades; however, its exploration as a possible anticancer chemotherapeutic has gained momentum very recently. Honokiol nucleus possesses an established anticancer profile as validated by numerous in vivo and in vitro studies that suggest inhibition, modulation, or regulation of various signaling pathways involved in tumorigenesis. Further research is warranted to translate these promising preclinical findings into effective and safe clinical treatments for cancer patients, potentially revolutionizing the field of cancer therapy.
 
The study was conducted by researchers from University of Petroleum & Energy Studies, Dehradun-India, Uttaranchal University-India, Al-Farabi Kazakh National University-Kazakhstan, King Khalid University-Saudi Arabia, Fırat University-Turkey, Universidad del Azuay-Ecuador and University of Medicine and Pharmacy of Craiova-Romania.
 
The study findings were published in the peer reviewed journal: Chemico-Biological Interactions.
https://www.sciencedirect.com/science/article/abs/pii/S0009279723004143
 
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