Tesis

Efek Neuroprotektif Hibiscus sabdariffa Linn pada Model Tikus Penuaan: Fokus pada Mekanisme Neuroinflamasi Melalui Kajian In Vivo dan In Silico = Neuroprotective Effects of Hibiscus sabdariffa Linn. on Hippocampus of Aging Mouse Models: A Focus on Neuroinflammatory Mechanisms Through In Vivo and In Silico Studies.

Memperlambat gangguan neurokognitif yang berkaitan dengan usia telah menjadi sebuah tantangan. Kami mengevaluasi efek Hibiscus sabdariffa Linn. (HSL) pada penuaan yang diakselerasi D-galaktosa dan diet tinggi lemak. Selain itu, kami mempelajari potensi mekanisme molekuler yang dapat bertanggung jawab atas efek anti-penuaan HSL. Sebanyak 48 tikus dibagi dalam 6 kelompok; 1 −kontrol muda (NM), 2−kontrol tua (NAg), 3−sonde D-galaktosa (AG1), 4−sonde D-galaktosa + diet tinggi lemak (AG2), 5−sonde D-galaktosa + HSL (AG1.H), dan 6−sonde D-galaktosa + diet tinggi lemak + HSL (AG2.H) selama 6 minggu. Semua tikus melakukan uji Y Maze untuk menilai fungsi memori kerja. Pengukuran marker inflamasi (NF-kB, TNF-α, IL-6, dan IL-10), BDNF, dan NfL telah dilakukan. Uji in silico zat aktif HSL terhadap protein inflamasi juga dianalisis. D-galaktosa dan diet tinggi lemak cenderung mengakibatkan gangguan fungsi memori kerja, dan terjadi peningkatan bermakna pada NF-kB, TNF-a dan NfL (p= 0,0024; < 0,0001; dan 0,0011) meskipun tidak terdapat pengaruh pada IL-6, IL-10, dan BDNF. HSL cenderung mencegah penurunan fungsi memori kerja pada model tikus penuaan dan menurunkan NF-kB, TNF-a, serta NfL. Pada uji in silico terdapat senyawa antosianin Cyanidin-3-rutinoside yang memiliki interaksi kuat terhadap protein NF-kB, TNF-α, dan IL-6. HSL berpotensi mengurangi neuroinflamasi pada penuaan dengan Cyanidin-3-rutinoside sebagai kandidat zat aktif HSL yang dapat berikatan langsung dengan sisi aktif sitokin pro-inflamasi.
Kata Kunci: Hibiscus sabdariffa Linn., Neuroinflamasi, Penuaan, Memori kerja, NfL


Slowing down age-related neurocognitive impairment has become a challenge. We evaluated the effects of Hibiscus sabdariffa Linn. (HSL) on D-galactose-induced aging and a high-fat diet. In addition, we studied the potential molecular mechanisms that could be responsible for the anti-aging effects of HSL. A total of 48 rats were divided into 6 groups: 1−young control (NM), 2−old control (NAg), 3−D-galactose (AG1), 4−Dgalactose + high-fat diet (AG2), 5−D-galactose + HSL (AG1. H), and 6−D-galactose + high-fat diet + HSL (AG2.H) by oral for six weeks. All rats performed the Y Maze test to assess working memory function. Measurements of inflammatory markers (NF-kB, TNF- α, IL-6, and IL-10), BDNF, and NfL have been performed. In silico tests of HSL active substances against inflammatory proteins were also analyzed. D-galactose and high-fat diets tended to result in working memory impairment, and there was a significant increase in NF-kB, TNF-a, and NfL (p= 0,0024; < 0,0001; and 0,0011) although there was no effect on IL-6, IL-10, and BDNF. HSL tends to prevent a decline in working memory function in aging mouse models and decreases NF-kB, TNF-a, and NfL. In the in silico test, the compound anthocyanin Cyanidin-3-rutinoside is the best candidate with strong interactions with NF-kB, TNF-α, and IL-6 proteins. HSL can potentially reduce neuroinflammation in aging with Cyanidin-3-rutinoside as a candidate for the active substance of HSL that can bind directly to the active side of pro-inflammatory cytokines.
Keywords: Hibiscus sabdariffa Linn., Neuroinflammation, Aging, Working memory, NfL