Phytochemical Profiling and Multi-Target Pharmacological Evaluation of Symphyotrichum squamatum Unveils Its Potential as a Source of Antidiabetic and Anti-Inflammatory Agents

Mohammed Hassan¹Islam Mostafa^1,2,3*Ahmed M Saad^4,5*Ahmed S. AbdelKhalek⁶Mahmoud M. Elaasser⁷Zepeng Yin^8,9Mahmoud Sitohy⁵Mohamed El-Sadek⁶Omer I. Fantoukh¹⁰Assem M. El-Shazly^1*Mona Fekry^1*

• ¹Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt, Zagazig, Egypt
• ²Pharmaceutical services center, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt, Zagazig, Egypt
• ³Clinical Pharmacy Program, Medical Sector, Zagazig National University, Tenth of Ramadan City, Egypt, Tenth of Ramadan, Egypt
• ⁴Zagazig University Faculty of Agriculture, Zagazig, Egypt
• ⁵Department of Biochemistry, Faculty of Agriculture, Zagazig University, Zagazig 44511, Egypt, Zagazig, Egypt
• ⁶Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt, Zagazig, Egypt
• ⁷Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo 11751, Egypt, Cairo, Egypt
• ⁸Key laboratory of fruit postharvest biology of Liaoning Province, Shenyang 110866, China, Shenyang, China
• ⁹College of Horticulture, Shenyang Agricultural University, Shenyang 110866, China, Shenyang, China
• ¹⁰Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia, Riyadh, Saudi Arabia

This study aimed to thoroughly profile the phytochemicals and pharmacological properties of the aerial parts of 658857 to assess its potential as a valuable source of natural therapeutic agents. The research focused on isolating and identifying bioactive compounds and evaluating their antioxidant, cytotoxic, antidiabetic, and anti-inflammatory effects. Chromatographic purification of the petroleum ether and ethyl acetate fractions led to the isolation of four compounds: 3β-Friedelinol, Spinasterol, Dioctyl phthalate, and Kaempferol-3,7-diglucopyranoside. Additionally, the LC/MS profile of the hydro-alcoholic extract identified 35 metabolites, indicating a diverse chemical profile rich in fatty acids, phenolic propanoids, and terpenoids. Quantitative assays confirmed the extract's abundance in phenolics (65.9 ± 3.6 mg GAE/g extract) and flavonoids (25.8 ± 1.1 mg QE/g extract), correlating with notable in vitro antioxidant activity, as shown by low SC₅₀ values of 77.00 µg/mL (DPPH) and 66.00 µg/mL (ABTS). The extract exhibited weak cytotoxicity against Hep-G2 and Panc-1 cell lines. Notably, both the extract and the isolated Kaempferol-3,7-diglucopyranoside demonstrated potent, dose-dependent inhibition of key carbohydrate-digesting enzymes, indicating antidiabetic activity. The flavonoid glycoside was particularly effective against α-amylase (IC₅₀ = 24.29 µg/mL). The extract also showed promising anti-inflammatory activity via COX-1 inhibition (IC₅₀ = 137.51 µg/mL). To explain these bioactivities, molecular docking studies were performed, revealing that essential compounds, namely Kaempferol-3,7-diglucopyranoside and dicaffeoylquinic acids, form stable, high-affinity interactions with the reactive locations of α-amylase, α-glucosidase, and COX enzymes. These findings collectively support S. squamatum as a promising candidate for further development in the management of diabetes and inflammation.