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Molecular insights for an anti-osteoporotic properties of Litsea glutinosa on Saos-2 cells: An in-vitro approach.

ABSTRACT: Osteoporosis is a skeletal disease that is identified by the deterioration of micro-architecture of bone tissue, leading to enhanced bone brittleness and a consequential increase in fracture threat. There are many treatments available for osteoporosis such as bisphosphonate therapy, hormonal replacement therapy, herbal therapy etc. For decades, there are several herbs that are attributed to have anti-osteoporotic effects however the candidate genes involved in it remained unknown. In line with this, the present study is focused to elucidate the anti-osteoporotic property of Litsea glutinosa (LG). To understand the proliferative effect and identify involved players, gene expression was studied on the Saos-2 osteocytes in-vitro. The expression profile of candidate genes involved in different signaling pathways such as Egr-2, RUNX2, MAPK3, NFATc1, CREB, ERβ, along with proliferation and apoptotic markers in osteoporosis were selected for the study. The gene expression profile demonstrated a significant up-regulation of Egr-2, RUNX2, MAPK3, CREB, EBβ in the range of 1.5-2.2 folds, whereas NFATc1 was found to be down-regulated up to 0.4 times compared to control when treated with 250 μg/mL of LG. Besides this, anti-apoptosis effect of LG was also supported by flow cytometry results which also proved that LG induces proliferation and inhibits apoptosis, suggesting the proliferative role of LG. In conclusion, the present study gathers the potency of LG extract for its proliferative and anti-apoptotic effect on Saos-2 osteocytes and opens a new avenue for detailing the mechanistic actions of it on mitigating the pathophysiology of osteoporosis.

SUBMITTER: Changani H

PROVIDER: S-EPMC8728066 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLitsea glutinosa (Lour.) C. B. Rob. belongs to the Litsea genus and is categorized under the family of Lauraceae. The study aimed to investigate the phytoconstituents and pharmacological properties of methanol extract of leaves of Litsea glutinosa, focusing on antidiabetic activity via in vivo and in silico techniques.MethodsExtensive chromatographic and spectroscopic techniques were applied to isolate and characterize the constituents from the L. glutinosa plant species. The antidiabetic activity was studied in streptozotocin-induced diabetes mice, and the computational study of the isolated compounds was carried out by utilizing AutoDock Vina programs. In addition, the pharmacokinetic properties in terms of absorption, distribution, metabolism and excretion (ADME) and toxicological profiles of the isolated compounds were examined via in silico techniques.ResultsIn the present study, two flavonoid glycosides 4΄-O-methyl (2 ̋,4 ̋-di-E-p-coumaroyl) afzelin (1) and quercetin 3-O-(2 ̋,4 ̋-di-E-p-coumaroyl)-α-L-rhamnopyranoside (2) were isolated from the leaves of L. glutinosa and characterized by 1H and 13C NMR, COSY, HSQC, HMBC, and mass spectral data. Although compounds 1 and 2 have been reported twice from Machilis litseifolia and Lindera akoensis, and Machilis litseifolia and Mammea longifolia, respectively, this is the first report of this isolation from a Litsea species. Administering the methanolic extract of L. glutinosa at doses of 300 and 500 mg/kg/day to mice with diabetes induced by streptozotocin led to a significant decrease in fasting blood glucose levels (p < 0.05) starting from the 7th day of treatment. Besides, the computational study and PASS analysis endorsed the current in vivo findings that the both isolated compounds exerted higher binding affinities to human pancreatic α-amylase and aldose reductase than the conventional drugs. The in silico ADMET analysis revealed that the both isolated compounds have a favorable pharmacokinetic and safety profile suitable for human consumption.ConclusionAccording to the current outcomes obtained from in vivo and in silico techniques, the leaf extract of L. glutinosa could be a natural remedy for treating diabetes, and the isolated phytoconstituents could be applied against various illnesses, mainly hyperglycemia. However, more investigations are required for extensive phytochemical isolation and pharmacological activities of these phytoconstituents against broader targets with exact mechanisms of action.

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Molecular insights for an anti-osteoporotic properties of Litsea glutinosa on Saos-2 cells: An in-vitro approach.

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