Rosmarinic acid extract with potent biological activities was successfully isolated by supramolecular technique and solvent extraction from Perilla leaves. By the supramolecular complex which was formed from flavocommelin and Perilla leaf extract as initial materials, the supernatant containing rosmarinic acid was isolated. Rosmarinic acid extract (62.9 ± 4.5% purity) was partly purified by partitioning ethyl acetate and water. Rosmarinic acid extract exhibited high total phenolic content of 433.9 ± 58.6 μg/mg of gallic acid equivalent, effective DPPH radical scavenging activity (SC50 of 5.5 ± 0.2 μg/mL), antiallergic activity (IC50 of 52.9 ± 6.7 μg/mL), and α-glucosidase inhibitory activity (IC50 of 0.23 ± 0.01 mg/mL). Rosmarinic acid extract shows high potential for diabetes mellitus and allergy treatments by inhibiting α-glucosidase activity and measuring β-hexosaminidase, related to life-style disease.

Methyl, propyl and hexyl esters of rosmarinic, caffeic and p-coumaric acids were tested for antiallergic activity, and rosmarinic acid propyl ester exhibited the greatest β-hexosaminidase release suppression (IC50, 23.7 μM). Quadratic correlations between pIC50 and cLogP (r(2) = 0.94, 0.98, and 1.00, respectively) were observed in each acid ester series. The antiallergic activity is modulated by hydrophobicity, and alkyl chain bulkiness.

Rosmarinic acid (RA), commonly found in Nepetoidae subfamily of Lamiaceae family, possesses various biological activities. To expand its application, RA was modified by esterification with methyl (me), propyl (pro), and hexyl (hex) alcohols and then tested antibacterial, α‐glucosidase inhibitory, and lipid accumulation suppression activities. Consequently, RA derivatives enhanced antibacterial activity, especially the RA‐pro and RA‐hex, which effectively inhibited the growth of Bacillus cereus rather than tannic acid, a natural antibacterial agent. RA‐hex also inhibited α‐glucosidase inhibitory activity greater than luteolin. By computational molecular docking, dihydroxyphenyl group and hexyl group were selected as essential groups for interaction with the active site of α‐glucosidase through hydrogen bonding and hydrophobic interaction, contributing to the great inhibitory activity. Furthermore, RA‐pro and RA‐hex effectively suppressed lipid accumulation of 3T3‐L1 cells, superior to EGCG, a well‐known anti‐obesity phytochemical. These biological effects of RA derivatives commonly attributed to hydrophobicity, hydrogen bonding, and steric bulkiness of the side chain. Practical applications Rosmarinic acid (RA), a fundamental compound in the family Lamiaceae, is one of powerful naturally occurring antioxidants as well as other biological activities. Furthermore, its abundance in nature was also high in amount in the plant kingdom. So, natural RA can be one of possible natural resources for creating potent natural drugs and biologically useful substances after chemical modification. Studies on various biological activities may intensively expand usage and application of RA. In this study, RA was derivatized to corresponding ester such as methyl, propyl, and hexyl alcohols with higher hydrophobicity, and found great antibacterial, α‐glucosidase inhibitory, and lipid accumulation suppression activities. RA‐pro and RA‐hex significantly suppressed lipid accumulation and cell differentiation. Therefore, RA derivatives with multiple biological activities have the potential to be applied in the food and pharmaceutical industries as food ingredients and supplements.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Silibinin is a flavonoid compound which has medicinal value. Previous studies revealed that silibinin exhibited an anti-fibrotic effect. However, whether silibinin could attenuate high-fat diet (HFD)-induced renal fibrosis remains unclear. Therefore, this study aimed to explore the molecular mechanism by which silibinin regulated renal fibrosis induced by HFD. Methods: In the present study, human renal glomerular endothelial cells (HRGECs) were treated with various concentrations of silibinin. Then, cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. In addition, HRGECs were exposed to 100 nM TGF-β1 for mimicking in vitro renal fibrosis. The expressions of collagen I, fibronectin, and α-SMA were detected by reverse transcription-quantitative polymerasechain reaction and Western blot. Protein levels of p-IκB and p-p65 were examined by Western blot; meanwhile, level of NF-κB was measured by immunofluorescence staining. Furthermore, HFD-induced mouse model of renal fibrosis was established. The mouse body weight, fasting glucose, kidney weight/body weight, microalbuminuria, kidney histopathology, and fibrotic area were measured to assess the severity of renal fibrosis. Results: Low concentration of silibinin (≤50 μM) had no cytotoxicity, while high concentration of silibinin (≥75 μM) exhibited significant cytotoxicity. Additionally, TGF-β1 increased the expressions of collagen I, fibronectin, α-SMA, p-IκB, and p-p65 and decreased the level NF-κB, while these effects were notably reversed by 50 μM silibinin. Moreover, both 50 and 100 mg/kg silibinin greatly decreased HFD-induced the upregulation of kidney weight/body weight, microalbuminuria, and fibrotic area. 100 mg/kg silibinin markedly reduced collagen I, fibronectin, and p-p65 expressions in mice renal tissues. Conclusion: Silibinin was able to attenuate renal fibrosis in vitro and in vivo via inhibition of NF-κB. These data suggested that silibinin may serve as a potential agent to alleviate the renal fibrosis of DN.