Magnolol.pptx It's natural drugs source still in process of discovery, part of pharmacy subject pharmacognosy

Pharmacognosy

1. Topic: Magnolol Course title: Natural Products Course code: Pharm-814 Submitted to: Dr Inam Ullah Submitted by: Marina Khan

2. Introduction: Magnolol (MG) is one of the primary active components of  Magnoliae officinalis  cortex, is a biphenyl-type neolignane. Tradationally used in Asian medicine, particular ly in traditional Chinese and Japanese herbal medicine. It possesses a wide range of pharmacological activities including anti-inflammatory antioxidant and neuroprotection.  In recent years, attention has been drawn to this component due to its potential as an anti-inflammatory and antitumor drug.

3. Botanical Source: Magnolol is derived from the root and branch bark of the magnolia tree Magnolia officinals , commonly found in China. Chemical structure: 5,5′-diallyl-2,2′-dihydroxy biphenyl

4. History MG was first isolated from magnolia bark by Japanese scientist Sugii in 1930 and was first synthesized by Swedish scientist H. Erdtman and J. Runebeng with the p-allylphenol as raw material. Physical Properties: Appearance: White to off white crystalline powder Melting Point: around 102 °C Magnolol a type of bisphenol compound, is a white fine powder with a spicy and fragrant smell. Solubility: Magnolol showed a lower solubility than honokiol at acidic pH values, but a higher solubility at alkaline pH values. Magnolol showed Poor aqueous solubility. Stability: Bioavailabilty : Low oral Bioavailability

5. Extraction: The highest content of magnolol was seen in roots of magnolol tree at a concentration of 87-96mg/g of extract. Various methods are used for extraction of magnolol from magnolia extract of bark roots and leaves that include traditional solvent extraction, supercritical fluid extracton , ultrasound assisted extraction, microwave assisted extraction.

6. Formulations: Magnolol has poor water solubility and low oral bioavailability which limits its use clinical use to improve these properties various formulation have been developed; Magnolol (MG) has poor water solubility and low oral bioavailability, which limits its clinical use. To improve these properties, various formulations have been developed: Liposomes: Encapsulate magnolol in lipid bilayers to enhance solubility and protect it from degradation (Shen et al., 2016). Solid Dispersions: Disperse magnolol in a solid matrix to improve its dissolution rate ( Stefanache et al., 2017a). Emulsions: Use a mixture of oil and water to improve magnolol's solubility (Sheng et al., 2014). Nanoparticles: Create tiny particles of magnolol to increase its surface area and bioavailability (Wang et al., 2011). These methods help make magnolol more effective when administered orally.

7. Pharmacological Activity: Anti-inflammatory activity: Magnolol reduces inflammation by inhibiting the production of pro-inflammatory cytokines and enzymes. It interferes with signaling pathways such as NF- κB , which is pivotal in the inflammatory response. This anti-inflammatory effect is beneficial in conditions like asthma, where magnolol can modulate immune cell infiltration and reduce airway inflammation​. Anti-tumor activity: Disease targeted Breast, lung colon and prostate cancer. Magnolol inhibits cancer cell proliferation and induces apoptosis through multiple pathways including the inhibition of the PI3K/Akt/mTOR, NF- κ B, and MAPK signaling pathways. It also disrupts the cell cycle and inhibits metastasis and angiogenesis​

8. 3. Antiangiogenesis activity: Magnolol shows significant pharmacological activities by inhibiting angiogenesis, a key process in diseases like cancer, rheumatoid arthritis, and diabetic retinopathy. It achieves this by regulating the PI3K/Akt/mTOR and HIF-1α/VEGF-dependent pathways and reducing ROS production. Additionally, magnolol suppresses tumor growth and venous remodeling by enhancing HO-1-mediated resistance to oxidative stress and blocking proteolytic activity. These mechanisms make magnolol a promising therapeutic agent for various conditions involving abnormal cell proliferation and angiogenesis.

9. 4. Cardiovascular Protection Magnolol exhibits cardiovascular protective effects by treating conditions such as coronary artery disease, hypertension, and dyslipidemia. It inhibits the migration and proliferation of vascular smooth muscle cells (VSMCs), demonstrating antiplatelet, antithrombotic, and antihypertensive activities. These effects are mediated through the inhibition of the MAPK family, Akt/ERK1/2/GSK3 β- catenin pathway, ACE/Ang II/AT-1R cascade, and the upregulation of PPAR- β/γ and NO/PKG pathways. Magnolol also reduces VSMC migration and proliferation by targeting pathways involving integrins, focal adhesion kinase, cyclins, and the renin-angiotensin system, and acts as a vasodilator by controlling iNOS and COX-2 expression levels.

10. 5.Hypoglycemic activity: Magnolol, from Magnolia species, treats Type 2 Diabetes Mellitus (T2DM). It enhances insulin sensitivity by inhibiting protein tyrosine phosphatase 1B (PTP1B) and activates AMPK and PPAR- γ, which regulate glucose metabolism. Magnolol also inhibits α- glucosidase, reducing carbohydrate absorption. These actions collectively improve glycemic control and manage T2DM effectively.

11. 6. Gastrointestinal Protection: Magnolol (MG) inhibits colonic muscle contractions by decreasing L-type Ca²⁺ channel activity. MG showed higher antidiarrheal activity than honokiol, likely due to its inhibition of the liver CYP450 enzyme

12. 7.Neuroprotection: Magnolol (MG) crosses the blood-brain barrier and has significant neuroprotective effects. It acts as a partial agonist of CB1 and CB2 receptors and enhances GABAergic neurotransmission. MG is more effective than honokiol in promoting PPAR-γ activity and shows strong antidepressant, anti-Alzheimer's, and antiepileptic properties by reducing inflammation, oxidative stress, and neuronal damage. It modulates several pathways, including NF- κB and PI3K/Akt, to protect the brain and improve cognitive functions

13. 8.Interaction with CYP-450 enzymes Magnolol (MG) inhibits various CYP450 enzymes in humans and rats, affecting drug metabolism. It strongly inhibits human CYP1A, CYP2C19, and rat CYP2C, CYP2B6, and CYP3A, with competitive inhibition for several CYPs. MG also inhibits CYP1A2 and CYP2C19, showing both competitive and noncompetitive inhibition. Different CYP450 isoforms show varied activities in metabolizing MG, necessitating further studies on its interactions with CYP substrate drugs.

14. 9.Antibacterial activity Magnolol (MG) demonstrates potent antibacterial activity against Aeromonas hydrophila and methicillin-resistant Staphylococcus aureus (MRSA), while also inhibiting Streptococcus mutans to prevent dental caries. Additionally, it exhibits antifungal effects against Candida spp. and Fusarium spp.

15. 10. Antioxident Properties In terms of antioxidant properties, MG scavenges peroxyl radicals, reduces myeloperoxidase (MPO) activity, and modulates pro-inflammatory cytokine expression to protect against oxidative stress-related conditions.

16. Besides these pharmacological activities mentioned above, MG also has the following activities: inhibition of osteoclast differentiation, antiphotoaging, antiparasitic, antiviral activity, and reduction of multidrug resistance.

17. Toxicity: Magnolol (MG) exhibits cytotoxicity at various concentrations and exposure durations in different cell lines, primarily affecting cell viability and inducing apoptosis. Studies indicate that MG concentrations ranging from 10 to 100 μM can affect normal hepatocytes, vascular smooth muscle cells (VSMCs), preadipocytes, and cancer cells, leading to decreased cell survival rates and increased apoptotic responses. MG also demonstrates dose-dependent inhibition of cell proliferation and growth in multiple cell types, including colon cancer, lung cancer, prostate cancer, gallbladder cancer, and ovarian cancer cells. However, it's worth noting that MG shows antimutagenic activity against UV-induced mutations and is generally considered nontoxic, with no mutagenic or genotoxic effects observed in various tests.