INTRODUCTION:

The African Tulip Tree (Spathodea campanulata) or the Flame of the Forest or Fountain Tree is a native, very fast-growing, evergreen tree of tropical West Africa. It belongs to family Bignoniaceae and is native to West Africa.

It gets another name as its unique red-orange flowers are trumpet-shaped, which are also referred to as the Flame of the Forest or Fountain Tree. This tree thrives in hot, moist climate regions and occurs widely across Asia, the Pacific Islands, the Caribbean, and Central and South America. Though its growth in cultivation is usually 10 to 20 meters (30 to 65 feet), it may reach as high as 30 meters (98 feet) in native forests. The flowers of the trees are tulip-shaped, containing sweet nectar, which draws birds and facilitates pollination. Its leaves, in contrast to tulips, are large, serrated, and glossy green. The tree produces abundant, lightweight, canoe-shaped seedpods containing numerous winged seeds. These seed pods enable the seeds to be carried away by wind currents.¹

Its dense crown makes the African Tulip Tree an attractive option as a shade tree in parks and gardens. In traditional medicine, its bark helps heal wounds, especially burns, and is used in medicinal purposes if Its foliage is considered to be invasive in some tropical climates due to its rapid expansion and competition with local flora. The tulip tree is known for its enormous growth and support of its shares, which can have concerning effects on the local ecosystem. Ecologically, the tree helps the pollinators.²

The many medicinal qualities of the African Tulip Tree (Spathodea campanulata) are attributed to its profusion of phytochemicals and phytocompounds. Alkaloids, flavonoids, tannins, saponins, sterols, and glycosides are important components. These substances have a number of biological characteristics, such as anti-inflammatory, antimicrobial, antioxidant, and analgesic effects, which support the plant's traditional uses in the treatment of fever, malaria, diabetes, stomach ulcers, wounds, and skin infections.³As an example, it has been proclaimed that Spathodea campanulata’s leaves have some anti-inflammatory activities and some kidney protective activity.¹¹Also, the flowers have some anti-inflammatory and diuretic effects; the leaves are included in the treatment of kidney disorders and urethra inflammation.⁵These findings underscore the plant's potential in traditional medicine and its therapeutic applications.

Key Constituents and Their Functions as per IMPPAT:

1. Flavonoids: Known for their antioxidant, anti-inflammatory, and antimicrobial effects, flavonoids support the plant’s traditional use in healing wounds and treating infections.⁴

2. Iridoids: The plant has long been used to treat infections and lessen inflammation, which may be explained by these compounds' potent anti-inflammatory, antimicrobial, and antioxidant qualities.⁵

3. Terpenoids: Aside from giving the plant its distinct aroma, terpenoids also have antimicrobial and anti-inflammatory effects, helping it fight off harmful pathogens.³

4. Steroids: The traditional use of Spathodea campanulata for pain management is supported by the fact that plant steroids, which are present in many medicinal plants, are well-known for their capacity to lower inflammation and relieve pain.

5. Cinnamic Acid Derivatives: These antioxidant-rich compounds also have antimicrobial properties, helping to protect the plant from environmental stress and infections.³

6. Cerebrosides: Scientists have recently discovered a new cerebroside called Campanulatoside in the stem bark, even though research on its health benefits is ongoing.⁶

7. Carotenoids: These potent antioxidants support the plant's general health benefits by scavenging dangerous free radicals.³

Spathodea campanulata has been used historically to treat convulsions, inflammation, diabetes, malaria, and wound healing because of these bioactive compounds. Its potential as an antibacterial, antifungal, and anti-inflammatory agent has been investigated scientifically, supporting some of its traditional applications.

The rich red, purple, and blue hues of many plants, including the African Tulip Tree (Spathodea campanulata), are caused by natural pigments called anthocyanins. In addition to their vivid colors, these substances have been extensively studied for possible health advantages.

Health Benefits of Anthocyanins:

1. Powerful Antioxidants: By scavenging dangerous free radicals, anthocyanins aid in the body's defense against chronic illnesses like cancer and heart disease.⁷

2. Fighting Inflammation: These organic substances have been found to reduce inflammation, a key factor in conditions such as heart disease and diabetes.⁷

3. Heart Health: Eating foods rich in anthocyanins has been linked to improved cholesterol levels and a lower risk of heart disease.

4. Brain Boost: Anthocyanins may improve memory and cognitive function, which could lower the risk of neurodegenerative diseases, according to research.⁸

5. Supporting Reproductive Health: Recent research suggests that anthocyanins could be beneficial to protect against reproductive harm caused by environmental pollutants like microplastics, shielding the body from hormone disruptions and tissue damage.

These health advantages can be reinforced by including foods high in anthocyanins, such as purple rice, blueberries, and other vibrantly colored fruits and vegetables in your diet. Although there is currently little information on the African Tulip Tree's anthocyanin content, its vibrant coloring indicates that it contains these healthy substances. Based on their established biological functions and previous research, we determined that the tyrosine kinase protein (PDB ID: 5M8M) is a major target for the antioxidant activity of these plant extracts.

It has been determined and confirmed that the anti-inflammatory properties of these phytochemicals, which are produced from particular plant extracts.⁹

The primary objective of in-silico research on the African Tulip Tree (Spathodea campanulata) is to use computational methods to investigate the interactions between its bioactive compounds and particular biological targets. It helps in studying the skin brightening activity of African tulip flowers. This aids scientists in comprehending the plant's potential for creating novel medicinal medications.
Before proceeding with lab-based (in-vitro) and animal (in-vivo) research, scientists can swiftly and economically identify promising drug candidates by employing in-silico techniques. This method aids in the creation of plant-based medications and is essential in the early phases of drug discovery.

MATERIAL AND METHOD:

In-silico studies rely on computational models to predict how bioactive compounds bind to biological targets. Molecular docking is a crucial method that aids in the visualization and analysis of these interactions. AutoDock Vina, a widely used docking tool, is favoured for its speed and accuracy in predicting how well a compound might fit into a target protein.

Steps:

1. Selection of Bioactive Compounds:

· The key phytochemicals found in Spathodea campanulata—such as flavonoids, alkaloids, anthocyanins, and tannins—are identified using databases like Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT).

· Their molecular structures (in 2D or 3D) are downloaded in SDF or MOL format and then converted to PDBQT format using tools like Open Babel or AutoDock Tools (ADT).

2. Selection of Target Proteins:

· The Protein Data Bank (PDB) is used to retrieve target protein (5M8M tyrosine kinase).

· After that, these proteins are prepared for docking by utilizing AutoDock Tools to optimize their structure, add hydrogen atoms, and remove water molecules.

3. Molecular Docking with AutoDock Vina:

· The chosen bioactive compounds (ligands) are set up for docking with the target protein (5M8M tyrosine kinase).

· A grid box is placed around the protein’s active binding site to define the docking area.

· AutoDock Vina is used for the docking process, and the binding affinity (measured in kcal/mol) is recorded to evaluate how well each compound interacts with the protein.

4. Analysis of Docking Results:

· The best-docked poses (those with the lowest binding energy, indicating the strongest interactions) are selected for further analysis.

· The interactions, such as hydrophobic and hydrogen bonding interactions, and electrostatic forces, are visualized using tools like PyMOL, Discovery Studio, or LigPlot+.

· Finally, the top-ranked compounds are chosen for further pharmacokinetic studies to assess their drug-like potential by using PreADMET software.

AutoDock Vina offers a cost-effective and efficient method for screening phytochemicals from the African Tulip Tree. This study helps in discovering new therapeutic compounds for drug development.

The crystal structure of human tyrosine kinase (5M8M), a crucial antioxidant enzyme that aids in preserving cellular redox balance, is represented by the 5M8M protein. It was chosen for molecular docking with Spathodea campanulata phytochemicals for a number of important reasons:

1. Antioxidant and Anti-Inflammatory Potential:

· 5M8M protein is an important antioxidant enzyme that shields cells from oxidative damage and aids in the neutralization of dangerous reactive oxygen species (ROS).

· The bioactive compounds in Spathodea campanulata—such as flavonoids, anthocyanins, and tannins— are renowned for having potent antioxidant qualities.

· Molecular docking with 5M8M allows us to study how these plant compounds interact with redox-regulating enzymes, potentially boosting the body's natural antioxidant defences.¹⁰

2. Role in Disease Prevention:

· Chronic illnesses like diabetes, cancer, heart disease, and neurodegenerative diseases are all significantly influenced by oxidative stress.

· If bioactive compounds from the African Tulip Tree bind effectively to 5M8M, they may influence its enzymatic activity, opening doors for potential therapeutic applications.⁹

3. Structural Features of 5M8M:

· One of the most important active sites in 5M8M is in charge of detoxifying reactive oxygen species (ROS). Plant compounds that can bind to this site and either improve or regulate its function can be found using molecular docking.

· The protein's high-resolution crystal structure (2.02Å, X-ray diffraction) makes it well-suited for precise docking studies.⁹

4. Potential Drug Discovery Insights:

· If the docking results show strong binding affinities, it suggests that Spathodea campanulata compounds could be promising candidates for antioxidant drug development.⁹

RESULTS AND DISCUSSION:

When a ligand binds to a target protein in a specific conformation, its interaction energy is measured using molecular docking scores. These scores help assess how well a compound fits into the protein’s binding site. The three-dimensional arrangement of the ligand’s atoms or functional groups determines the strength of these interactions. Stronger and more favorable interactions are generally indicated by a higher negative docking score, whereas weaker or repulsive interactions are suggested by a higher score.

Table No. 1: Molecules with binding score rmsd value:

Molecule	Binding score	Rmsd	Remarks
Catechin	-9.3	0.000	Best binding affinity, strongest interaction.
Naringin	-8.3	0.000	Strong binding, potential bioactive compound.
Caffeic acid	-7.1	0.000	Moderate binding, good antioxidant potential.
Ajugol	-7.0	0.000	Moderate binding, possible biological activity.
Phytol	-6.5	0.000	Weaker binding, but still significant.
Alpha	-6.2	0.000	Moderate binding interaction.
Kojic acid	-5.9	0.000	Weakest binding, least favourable interaction.

· Catechin (-9.3kcal/mol) has the strongest binding affinity, making it the best candidate for further analysis.

· Niranjinin (-8.3kcal/mol) and Caffeic Acid (-7.1 kcal/mol) also show good binding potential, implying that they could have biological relevance.

· KOJIC ACID (-5.9kcal/mol) has the weakest binding, meaning it may not be a strong inhibitor of the target protein.

· The compounds with lower binding scores (more negative values), like Catechin and Niranjinin, are the most promising applicants for further pharmacological studies.

Figure no. 1: Ajugol showing hydrogen bonds

Figure no. 2: Catechin showing hydrogen bonds

Figure no. 3: Caffeic acid showing hydrogen bonds

· Ajugol forms hydrogen bonds with important residues ARG A:321 and ASN A:378 through its strong binding to 5M8M, which is essential for the protein's function.

· By establishing robust hydrogen bonds with TYR A:226, GLN A:236, and TRP A:117, catechin demonstrates a high binding affinity.

· The catechin-protein complex is further stabilized by pi-alkyl interactions, which aid in its safe retention in the active site.

· The short hydrogen bond distances (1.77 Å - 2.84 Å) indicate strong, stable interactions, highlighting Catechin’s potential as a bioactive molecule for targeting PRDX5.

· Caffeic Acid also forms three conventional hydrogen bonds, demonstrating a strong affinity for the 5M8M protein.

Table no. 2: Characteristics of different constituents:

Sr no.	Feature	Ajugol	Catechin	Caffeic acid
1.	Strongest interaction	ARG A:321 (1.96Å)	TYR A:226 (1.77 Å)	GLN A:236 (2.43Å)
2.	Total H-Bonds	2	3	3
3.	Pi- Interactions	None	Pi-Donor H-Bond	Pi-Sigma, Pi-Alky
4.	Binding Stability	Moderate	Strong	Strong
5.	Potential Drug Likeness	Moderate	High	High

ADMET PROPERTIES:

Table no. 3: ADMET properties of different constituents:

Sr. No.	Properties	Ajugol	Catechin	Caffeic acid
1.	BBB	0.0541798	0.394913	0.4976
2.	Buffer_solubility_mg_L	96016.3	2253.95	200243
3.	Caco2	6.35451	0.656962	21.1076*
4.	CYP_2C19_inhibition	Inhibitor	Inhibitor	Non
5.	CYP_2C9_inhibition	Inhibitor	Inhibitor	Inhibitor
6.	CYP_2D6_inhibition	Non	Non	Non
7.	CYP_2D6_substrate	Non	Non	Non
8.	CYP_3A4_inhibition	Inhibitor	Inhibitor	Inhibitor
9.	CYP_3A4_substrate	weakly	weakly	Non
10.	HIA	17.774012	66.707957	82.301311
11.	MDCK	0.528119	44.3849	109.433
12.	Pgp_inhibition	Non	Non	Non
13.	Plasma_Protein_Binding	22.083431	100.000000	40.290625
14.	Pure_water_solubility_mg_L	247916	1240.55	4878.52
15.	Skin_Permeability	-4.96798	-4.29301	-2.66994
16.	SKlogD_value	-2.575230	1.845850	0.569710
17.	SKlogP_value	-2.575230	1.845850	1.817710
18.	SKlogS_buffer	-0.559670	-2.109860	0.045900
19.	SKlogS_pure	-0.147710	-2.369190	-1.567370

CONCLUSION:

This in-silico study explored the therapeutic potential of bioactive compounds from Spathodea campanulata (African Tulip Tree) by analyzing their interactions with 5M8M (human peroxiredoxin 5, PRDX5) using AutoDock Vina. The results revealed that Ajugol, Catechin, and Caffeic Acid exhibited strong binding affinities, primarily stabilized by hydrogen bonding, pi-interactions, and hydrophobic forces. The most hydrogen bonds were formed by caffeine (GLN A:236 and GLU A:232), which ensured a stable interaction. Catechin also showed strong binding, which makes it a promising candidate for additional study. Since PRDX5 plays a role in the regulation of oxidative stress, these substances may have anti-inflammatory, antioxidant, or neuroprotective qualities that could be useful in the treatment of diseases like cancer, cardiovascular disorders, and neurodegenerative diseases. To validate these findings, further molecular dynamics simulations, ADMET analysis, and in-vitro studies are required to assess their stability, pharmacokinetics, and biological significance. Ultimately, this research highlights the potential of Spathodea campanulata bioactives, particularly Catechin and Caffeic Acid, as promising natural therapeutic agents for combating oxidative stress-related diseases.

ACKNOWLEDGMENT:

I would like to express my heartfelt gratitude to all those who supported me throughout the course of this research.

First and foremost, I am deeply thankful to my research guide, Prof. Shital Kalekar, Assistant Professor, School of Pharmacy, D.Y. Patil University, Ambi, Pune, for their invaluable guidance, constant support, and encouragement throughout this project. Their expertise, patience, and insightful feedback have played a crucial role in shaping this research work.

I would also like to extend my sincere thanks to our respected Principal, Dr. Atul Deshmukh, Principal, School of Pharmacy, D.Y. Patil University, Ambi, Pune, for providing the necessary facilities, motivation, and an academic environment that made this work possible.

CONFLICT OF INTEREST:

The authors declare that there is no conflict of interest regarding the publication of this research paper.

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Received on 11.04.2025 Revised on 19.05.2025

Accepted on 30.06.2025 Published on 24.07.2025

Available online from July 28, 2025

Res. J. Pharmacognosy and Phytochem. 2025; 17(3):209-213.

DOI: 10.52711/0975-4385.2025.00034

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