Gastrodin attenuates lipopolysaccharide‑induced inflammation and oxidative stress, and promotes the osteogenic differentiation of human periodontal ligament stem cells through enhancing sirtuin3 expression

Abstract

Periodontitis is a common inflammatory gum disease that destroys the periodontal tissue. Gastrodin (GAS) is the predominant bioactive component of Gastrodia elata Blume and exhibits anti-inflammatory, anti-apoptotic and antioxidant effects in various diseases, including bone-related diseases. The aim of the present study was to investigate whether GAS could protect lipopolysaccharide (LPS)-treated human periodontal ligament stem cells (hPDLSCs) against injury and inflammation, and to determine the potential underlying mechanisms. hPDLSCs were treated with LPS and GAS, alone or in combination, and cell viability, inflammation, oxidative stress levels and apoptosis were analyzed using a Cell Counting Kit-8 assay, ELISA assay, western blotting and flow cytometry, respectively. The osteogenic differentiation capacity was evaluated using an alkaline phosphatase (ALP) assay and Alizarin Red S staining. Sirtuin 3 (SIRT3) was silenced in cells treated with LPS and GAS to verify the involvement of SIRT3 in the effects of GAS. The results demonstrated that LPS-induced decrease in cell viability was rescued by treatment with 1, 10 or 50 µM GAS. The LPS-induced production of proinflammatory cytokines and increased level of oxidative stress were also inhibited following treatment with 50 µM GAS. Furthermore, GAS significantly promoted ALP activity, increased the number of mineralized nodules and increased the expression of proteins involved in osteogenic differentiation, including ALP, Runx2, osteocalcin and osteopontin, after osteoinduction, which were all downregulated following LPS stimulation. In addition, GAS prevented LPS-induced cell apoptosis and restored the imbalance of anti-apoptotic and proapoptotic proteins in hPDLSCs. In addition, SIRT3 knockdown significantly inhibited the protective effect of GAS on LPS-induced hPDLSC injury. In summary, the findings form the present study suggested that GAS may protect hPDLSCs from LPS-induced inflammation, apoptosis and oxidative stress, as well as promote their osteogenic differentiation. The effect of GAS on the osteogenic differentiation of hPDLSCs may therefore depend on the upregulated expression of SIRT3.

Chemistry, Biological Activities, and Pharmacological Properties of Gastrodin: Mechanism Insights

“…In a recent study, researchers showed that gastrodin reduced inflammation in kidney cells exposed to a hyperglycemic environment. [87] Finally, Feng et al [14] indicated that gastrodin enhanced the expression of sirtuin 3 (SIRT3). The enzyme that is crucial in regulating the inflammatory response and oxidative stress, as well as governing cell differentiation, is called Nuclear factor kappa B (NF-kB).…”

“…The enzyme that is crucial in regulating the inflammatory response and oxidative stress, as well as governing cell differentiation, is called Nuclear factor kappa B (NF-kB). [14] It also promoted the osteogenic differentiation of human periodontal ligament stem cells (HPLSC). In conclusion, gastrodin demonstrated potential anti-inflammatory activity by inhibiting the production of proinflammatory cytokines, suppressed immune cell activation, inhibited the expression of COX-2 and iNOS enzymes, and regulated the NF-kB signaling pathway.…”

“…Gastrodin a phenolic glycoside isolated from Gastrodia elata Blume is considered a traditional Chinese herbal medicine used to manage neurological disorders such as epilepsy, [1,2] dizziness, [3] and stroke. [4] Gastrodin showed antiinflammatory, [5][6][7][8][9][10] antioxidant, [11][12][13][14] anti-cancer, [15][16][17][18][19][20] and neuroprotective properties. [21][22][23][24][25][26][27] In recent years, many studies were conducted on the chemical nature, sources, and characterization of gastrodin, as well as its different biological properties.…”

“…[32] Additionally, gastrodin inhibited apoptosis and protected cells against oxidative stress-induced damage. [14] Moreover, gastrodin exerted therapeutic effects on various neurological disorders, including cerebral ischemia-reperfusion injury, [33] depression, [34] epilepsy, [35] and Tourette syndrome. [27] In animal studies, gastrodin reduced cerebral infarction, [33] inhibited microglia activation, [18] enhanced the ability to learn and overcome memory impairment, and inhibited the activation of TLR/MAPK and TLR/NF-kB signaling in the striatum.…”

Diosgenin prevents periodontitis by inhibiting inflammation and promoting osteogenic differentiation

“…LPS can activate the immune response and induce the expression of pro‐inflammatory cytokines such as tumor necrosis factor α (TNF‐α), interleukin (IL)‐1β, and interleukin (IL)‐6, resulting in periodontal inflammation and bone resorption (Ding et al, 2017). Under inflammation conditions, hPDLSCs suffer long‐term hypoxia and ischemic conditions, which greatly attenuates their abilities to self‐renew and perform osteogenesis (An et al, 2016; Feng, 2022). Many transcription factors and cellular signaling pathways are involved in the expression of pro‐inflammatory mediators (Diomede et al, 2017; Park et al, 2012; Zhao et al, 2020).…”