The Healing Potential of Jackfruit Leaves: A Study on Bioactive Compounds and Their Applications

Medicinal plants play a vital role in the development of pharmaceutical and cosmetic products, serving as a rich source of bioactive compounds. These natural substances, such as flavonoids, terpenoids, and phenolic acids, possess potent antioxidant and anti-inflammatory properties, making them valuable in the treatment of chronic diseases and the enhancement of skin health.

Flavonoids, one of the largest groups of polyphenolic compounds, have been extensively studied for their ability to scavenge free radicals and regulate oxidative stress. Oxidative stress is a key factor in chronic diseases like cancer, cardiovascular disorders, and neurodegenerative diseases, and antioxidant compounds from plants can mitigate these effects by bolstering the body’s natural defense systems. Flavonoids and terpenoids also exhibit enzyme inhibitory properties, offering therapeutic potential against various physiological processes.

Exploring Artocarpus heterophyllus Leaf Extracts

This study delves into the bioactive compounds present in Artocarpus heterophyllus (jackfruit) leaf extracts, using ethyl acetate and ethanol solvents for extraction. The choice of these solvents is based on their polarity, which significantly influences the efficiency and range of compound extraction.

Techniques like Thin Layer Chromatography (TLC) and Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) were employed to identify and characterize the major compounds in the extracts. The study also evaluated the extracts’ antioxidant activity to assess their potential in reducing oxidative stress. Additionally, the tyrosinase inhibitory activity of the extracts was studied for its relevance in cosmetic applications, particularly in skin pigmentation control.

Extraction Methods and Analysis

Plant Material Collection

Artocarpus heterophyllus leaves were collected in August 2024 from Kota Bandung, West Java, Indonesia. The plant specimens were authenticated at the Herbarium Bandungense, and the voucher number 8366/IT1.C11.2/TA.00/2024 was assigned for documentation and future reference.

Extract Preparation

Leaves were extracted using the maceration method with ethyl acetate (16 L) over 3–5 days to yield two batches of a viscous ethyl acetate extract weighing 6.078 g and 25.573 g, respectively. Ethanol was used to extract another sample (10 L over 3–5 days), resulting in ethanolic extracts weighing 15.8 g and 26.4579 g. Both extracts were monitored with TLC and isolated for further study.

LC-MS/MS Analysis

Each isolated compound was dissolved in methanol, and a 1-microliter aliquot was injected into the column for liquid chromatography with a gradient elution. The data were processed with UNIFI software, utilizing a screening solution workflow to facilitate automatic data handling and positive identifications.

Identification of Key Compounds

Chemical Composition

The prominent compounds in the ethyl acetate extract were identified as Cintramide, Licoflavone C, and 3,4,5-trimethoxy cinnamic acid. In the ethanol extract, the primary compound was (2s)-2-[(4-{1-hydroxy-3-imino-4h,5h,6h,6ah,7h,9h-imidazo[1,5-f]pteridin-8-yl}phenyl)formamido]pentanedioic acid, along with secondary compounds like Licoflavone C and (2s)-3-{[2-(4-hydroxyphenyl)acetyl]oxy}-2-methylpropanoic acid.

Molecular Docking Study

Molecular docking simulations revealed that compounds such as Cycloaltilisin 7 and Sitosterol exhibited strong binding affinities towards enzymes like fibroblast collagenase, elastase, MITF, MMP-1, and MMP-2. These findings suggest these compounds have significant potential as enzyme inhibitors.

Molecular Dynamics Simulation

Molecular dynamics simulations were conducted to assess the stability and structural flexibility of the Artocarpin and Sitosterol complexes with MMP-2. Artocarpin maintained a more stable binding compared to Sitosterol, which had higher RMSD and Rg values. Despite this, Sitosterol showed stronger interactions with several targets, particularly MMP-2 and MMP-13.

Antioxidant and Tyrosinase Inhibitory Activities

Antioxidant Activity

The ethyl acetate extract demonstrated a higher antioxidant activity of 117.64 ppm compared to the ethanol extract at 56.50 ppm. Ascorbic acid, used as a standard, had an activity of 5.39 ppm, highlighting the weaker antioxidant potential of the plant extracts.

Tyrosinase Inhibition

The ethanol extract exhibited a significant tyrosinase inhibitory activity of 177.24 ppm, much higher than the ethyl acetate extract at 97.16 ppm. Kojic acid, a standard inhibitor, had an activity of 45.96 ppm, suggesting that the ethanol extract is highly effective in inhibiting tyrosinase, making it valuable for cosmetic applications.

Conclusion

The study underscores the medicinal value of Artocarpus heterophyllus leaf extracts, highlighting their rich bioactive profile. The extracts exhibit promising antioxidant and anti-inflammatory properties, with potential applications in both pharmaceuticals and cosmetics. Further research could explore the use of these extracts in developing natural alternatives to traditional medications and skincare products.

Figure 2 LC-MS/MS chromatogram of compounds identified from the isolates of Artocarpus heterophyllus ethyl acetate and ethanol extracts.

Figure 3 The molecular interactions of MMP-13 with Artocarpin and Sitosterol as predicted inhibitory compounds within Artocarpus heterophyllus extracts.

Figure 4 Comparative molecular dynamics analysis of Artocarpin and Sitosterol complexes with MMP-2.

Figure 5 DPPH radical scavenging and tyrosinase inhibitory activities of Artocarpus heterophyllus leaf extracts.

Acknowledgments

This work was supported by a grant from the Ministry of Education, Culture, Research, and Technology (Kemendikbudristek) of Indonesia under Contract Number: 305/B.04/Rek/VI/2024. We extend our gratitude for their funding and support, which made this research possible.

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