| Title | Upgrading Isoquercitrin Concentration via Submerge Fermentation of Mulberry Fruit Extract with Edible Probiotics to Suppress Gene Targets for Controlling Kidney Cancer and Inflammation |
|---|---|
| Author | Md. Rezaul Karim1,2†, Safia Iqbal1,3†, Shahnawaz Mohammad4, Jong‑Hoon Kim5, Li Ling6, Changbao Chen6, Abdus Samad4, Md. Anwarul Haque2, Deok‑Chun Yang1,7, Yeon Ju Kim4*, and Dong Uk Yang1,8* |
| Address | 1Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin 17104, Republic of Korea, 2Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh, 3Department of Microbiology, Varendra Institute of Biosciences, Affiliated University of Rajshahi, Natore, 6400 Rajshahi, Bangladesh, 4Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin 17104, Republic of Korea, 5Department of Biotechnology, Pukyong National University, Busan 48513, Republic of Korea, 6Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, People’s Republic of China, 7Hanbangbio Inc., Yongin 17104, Republic of Korea, 8AIBIOME, Daejeon 34052, Republic of Korea |
| Bibliography | Journal of Microbiology, 62(10),919–927, 2024, |
| DOI | 10.1007/s12275-024-00163-8 |
| Key Words | Kidney cancer · Submerge fermentation · Phenolics · Flavonoids and antioxidant assay · HPLC · Cell viability assay · Gene expression |
| Abstract | In recent years, kidney cancer has become one of the most serious medical issues. Kidney cancer is treated with a variety of active compounds that trigger genes that cause cancer. We identified in our earlier research that isoquercitrin (IQ) can activate PIK3CA, IGF1R, and PTGS2. However, it has a very low bioavailability because of its lower solubility in water. So, we utilized sub-merge fermentation technology with two well-known probiotics, Lactobacillus acidophilus and Bacillus subtilis, as a microbial source and mulberry fruit extract as a substrate, which has a high IQ level to improve IQ yield. Furthermore, we compared the total phenolic, flavonoid, and antioxidant contents of fermented and non-fermented samples, and we found that the fermented samples had greater levels than non-fermented sample. In addition, the high-performance liquid chromatography (HPLC) results showed that the fermented mulberry fruit extract from B. subtilis and L. acidophilus showed higher IQ values (190.73 ± 0.004 μg/ml and 220.54 ± 0.007 μg/ml, respectively), compared to the non-fermented samples, which had IQ values (80.12 ± 0.002 μg/ml). Additionally, at 62.5 μg/ml doses of each sample, a normal kidney cell line (HEK 293) showed higher cell viability for fermented and non-fermented samples. Conversely, at the same doses, the fermented samples of L. acidophilus and B. subtilis in a kidney cancer cell line (A498) showed an inhibition of cell growth around 36% and 31%, respectively. Finally, we performed RT and qRT PCR assay, and we found a significant reduction in the expression of the PTGS2, PIK3CA, and IGF1R genes. We therefore can conclude that the fermented samples have a higher concentration of isoquercitrin, and also can inhibit the expression of the genes PTGS2, PIK3CA, and IGF1R, which in turn regulates kidney cancer and inflammation. |