Brill profit levels and organic growth in line with expectations, integration V&R according to plan and continuation of eBusiness growth Update on year-to-date performance During the third quarter Brill's eBusiness continued its strong growth, driven by eBooks and digital primary sources. This growth compensated for the ongoing decline in print books. YTD Journal sales declined mainly due to delayed invoicing, which is expected to be recovered in Q4, and continuing IT problems at our UK based distributor. Overall Brill's revenues including the acquisition of Vandenhoeck & Ruprecht and Böhlau Verlag (V&R) are clearly ahead of last year.Cost of goods sold improved slightly as a result of the migration from print to eBooks. Operating costs were in line with expectations. Year to date EBITDA, operating profit and net profit have developed as planned.The integration of V&R runs according to plan. Both the Brill as well as the V&R teams and staff are now part of one global matrix organization. Various integration projects in IT, production, distribution, publishing and sales are underway. Management closely leads and monitors the integration and is pleased with the progress and the results of the acquired V&R business so far.In August, Brill acquired the journal Folia Primatologica from Karger Publishing, an important addition to our Biology portfolio. At the end of Q3 Brill's Book Archive was launched, a digital archive expanding our eBook list with more than 6,000 back list titles in 2021. The first sales are expected in Q4. FY OutlookThe COVID-19 pandemic continues to make market circumstances difficult and unpredictable. In Asia important countries are still in lockdown and (intercontinental) travel is still difficult or impossible, limiting our staff to visit authors, conferences and customers in person. The shortages in the global supply chains are hampering Brill as well, to the extent that this may have a negative impact on the results of the important 4 th quarter and could affect our top-and bottom line negatively.

BACKGROUND: At present, there are many drugs used to manage diabetes including dipeptidyl peptidase-4 (DPP-IV) inhibitors which target insulin secretion. Abelmoschus manihot L. Medic, an endemic species of Minahasa, Indonesia, has been used as an antidiabetic herbal medicine. AIM: In this study, we studied its metabolites activities, in silico and in vitro, as inhibitor for DPP-IV, thus regulating insulin secretion. RESULTS: Of 38 identified metabolites, when docked into the catalytic site DPP-IV, 10 showed good binding energy within range of the standard gliptin drugs, that is, hibiscetin, gossypentin, gossypetin - 3-glucoside, myricetin, myricetin 3-glucoside, alpha spinasterol, quercetin, syringaresinol, stigmasterol, and isoquercetin. Three of those ten metabolites showed Ki within standard drugs values, that is, gossypetin, alpha spinasterol, and stigmasterol. The profile of molecular dynamic simulation, total energy and root mean square deviation of those metabolites were all similar with the standard gliptin drugs and predicted good stability of the complexes. The subsequent in vitro assay determining DPP-IV activity of the red Gedi leaves extract demonstrated that indeed the extract inhibited DPP-IV activity with IC50 860.67 μg/mL. Further studies are ongoing to prove the antidiabetic properties of the whole as well as isolated single compounds of the extract in particular gossypetin, alpha spinasterol, and stigmasterol as DPP-IV inhibitors. CONCLUSION: Our in silico studies showed that the compounds of ethanolic extract of red Gedi leaves potentially serve as DPP-IV inhibitors. Based on computed binding affinity, Ki, total energy, RMSD, and stability, the most potent compounds of the extract to inhibit DPP-IV activity are probably gossypetin, alpha spinasterol, and stigmasterol.

Abelmoschus manihot L. Medic, commonly called ‘‘red gedi’’, is an endemic species of Minahasa, Indonesia. The leaves of red gedi have been widely used in ethnomedicine and functional food as an antidiabetic. In this study, the ethanolic extract of the red gedi leaves was characterized by using liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (LC–ESI-MS). Compounds identified were phenolic acid derivates, flavonoids, terpenoids, phytosterols, alkaloids, and lignans. The most abundant flavonoids in the extract sample were quercetin derivatives. In total, 38 metabolite compounds were identified in red gedi leaves and were reported for the first time, including alpha spinasterol which is newly identified in this particular Abelmoschus species.