Anti-COVID-19, Anti-Inflammatory, and Anti-Osteoarthritis Activities of Sesamin from Sesamum indicum L

Abstract

During the COVID-19 (coronavirus disease 2019) outbreak, many people were infected, and the symptoms may persist for several weeks or months for recovering patients. This is also known as "long COVID" and includes symptoms such as fatigue, joint pain, muscle pain, et cetera. The COVID-19 virus may trigger hyper-inflammation associated with cytokine levels in the body. COVID-19 can trigger inflammation in the joints, which can lead to osteoarthritis (OA), while long-term COVID-19 symptoms may lead to joint damage and other inflammation problems. According to several studies, sesame has potent anti-inflammatory properties due to its major constituent, sesamin. This study examined sesamin's anti-inflammatory, anti-osteoarthritis, and anti-COVID-19 effects. Moreover, in vivo and in vitro assays were used to determine sesamin's anti-inflammatory activity against the RAW264.7 and SW1353 cell lines. Sesamin had a dose-dependent effect (20 mg/kg) in a monoiodoacetic acid (MIA)-induced osteoarthritis rat model. Sesamin reduced paw swelling and joint discomfort. In addition, the findings indicated that sesamin suppressed the expression of iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) in the RAW264.7 cell line within the concentration range of 6.25-50 μM. Furthermore, sesamin also had a suppressive effect on MMP (matrix metalloproteinase) expression in chondrocytes and the SW1353 cell line within the same concentration range of 6.25-50 μM. To examine the anti-viral activity, an in silico analysis was performed to evaluate sesamin's binding affinity with SARS-CoV-2 RdRp (severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase) and human ACE2 (angiotensin-converting enzyme 2). Compared to the controls, sesamin exhibited strong binding affinities towards SARS-CoV-2 RdRp and human ACE2. Furthermore, sesamin had a higher binding affinity for the ACE2 target protein. This study suggests that sesamin shows potential anti-SARS-CoV-2 activity for drug development.

Keywords: SARS-CoV-2 RdRp; anti-COVID-19; anti-inflammatory; anti-osteoarthritis; human ACE2; molecular docking.

Figure 1

Chemical structures of sesamin.

Figure 2

The timeline for monoiodoacetate (MIA)-induced osteoarthritis model. MIA: 50 μL (80 mg/mL). (A) Paw edema test. (B) Hind-limb weight-bearing test.

Figure 3

Cell viability, using the MTT assay, of three cell lines after 24 h of culture in the presence of different concentrations of sesamin.

Figure 4

(A) Sesamin’s anti-inflammatory effect using LPS-induced RAW264.7 cells for 24 h. Quantitation of iNOS and COX-2 protein expression. Blank contained the medium only, control received LPS (500 ng/mL), and drug-treated groups received doses of 12.5, 25, and 50 μM sesamin + LPS (500 ng/mL). (B) Sesamin’s anti-inflammatory effect using IL-1β-stimulated chondrocyte cells for 24 h. Quantitation of iNOS, MMP-3, MMP-13 protein expression. Blank contained the medium only, control received IL-1β (10 ng/mL), and drug-treated groups received doses of 12.5, 25, and 50 μM sesamin + IL-1β (10 ng/mL). (C) Sesamin’s anti-inflammatory effect using IL-1β-induced SW1353 cells for 24 h. Quantitation of MMP-13 protein expression. Blank contained the medium only, control received IL-1β (10 ng/mL), and drug-treated groups received doses of 12.5, 25, and 50 μM sesamin + IL-1β (10 ng/mL).

Figure 5

Paw edema volume was measured in MIA-injected rats on the second day. Positive control (P.C.) is indomethacin (2.5 mg/kg), LD: sesamin (5 mg/kg), MD: sesamin (10 mg/kg), HD: sesamin (20 mg/kg). Control group compared to a blank group: ### p < 0.0001. Sesamin and indomethacin groups compared to the control group: *** p < 0.001.

Figure 6

Paw edema volume was measured in MIA-injected rats on the second day. Positive control (P.C.) is indomethacin (2.5 mg/kg), LD: sesamin (5 mg/kg), MD: sesamin (10 mg/kg), HD: sesamin (20 mg/kg). Control group compared to blank group: ### p < 0.0001. Sesamin and indomethacin groups compared to control group: *** p < 0.001.

Figure 7

Cartilage histology and immunohistochemistry. H&E-stained knee joints. The positive control is indomethacin (2.5 mg/kg), LD: sesamin (5 mg/kg), MD: sesamin (10 mg/kg), HD: sesamin (20 mg/kg). The yellow circles represent the presence of cavities, while the red circles indicate the grouping of cells exhibiting intense staining. The black arrow indicates the existence of cartilage.

Figure 8

Molecular docking of sesamin with COVID−19 RdRp protein: (A) viral RdRp−sesamin complex, (B) two–dimensional interaction display, (C) Ramachandran plot of unbound protein, (D) hydrophobic and (E) hydrophilic properties of binding pocket, (F) Ramachandran plot of ligand−interacting amino acid residues.

Figure 9

Molecular docking of sesamin with ACE2: (A) ACE2−sesamin complex, (B) two−dimensional interaction display, (C) Ramachandran plot of unbound protein, (D) hydrophobic and (E) hydrophilic properties of binding pocket, (F) Ramachandran plot of ligand−interacting amino acid residues.

Figure 10

Pharmacophore descriptor of sesamin.

Figure 11

Molecular dynamics analysis of sesamin−SARS-CoV-2 RdRp complex. (A) Amino acid residues of apoprotein RMSF values and ligand-bound protein. Three-dimensional models of (B) changes in apoprotein in 0 ns (yellow) and 10 ns (red) and (C) changes in ligand-bound protein in 0 ns (yellow) and 10 ns (teal) and (D) overlap model of apoprotein (red) and ligand-bound protein (teal).

Figure 12

Molecular dynamics analysis of sesamin–human ACE2 complex. (A) Amino acid residues of apoprotein RMSF values and ligand-bound protein. Three-dimensional models of (B) changes in apoprotein in 0 ns (yellow) and 10 ns (red) and (C) changes in ligand-bound protein in 0 ns (yellow) and 10 ns (teal) and (D) overlap model of apoprotein (red) vs. ligand-bound protein (teal) at 10 ns.

Figure 13

Pharmacokinetic properties of the compounds.