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In inflammatory diseases, the expression of the target protein tumor necrosis factor‐alpha (TNF‐α) plays a crucial role in the pathogenesis and development of certain conditions, such as autoimmune diseases, rheumatoid arthritis, inflammatory bowel disease, and psoriatic arthritis. TNF‐α inhibitors have several limitations. Screening studies of plant‐derived compounds have shown promising results due to their lower incidence of side effects and reasonable cost. Therefore, this research focuses on identifying compounds isolated from Isodon coetsa, collected from previous studies, that exhibit inhibitory effects on TNF‐α through computational methods such as molecular docking and ADMET prediction. Among the compounds binding to the active site of TNF‐α, five diterpenoids, namely 2α,3α,24‐trihydroxy‐11α,12α‐epoxy‐urs‐20(30)‐en‐28,13β‐olide,2α,3α,24‐trihydroxy‐12,20(30)‐ursadien‐28‐oic acid, xerophilusin B, oridonin, and 15α‐hydroxy‐6,7‐seco‐1α,7:11α,6‐diolide‐ent‐kaur‐16‐en, exhibited higher binding affinity than the reference inhibitor SPD‐304. All the potential compounds predicted by ADME demonstrated favorable pharmacokinetic properties. Moreover, regarding the toxicity of the I. coetsaderived compounds, namely 2α,3α,24‐trihydroxy‐11α,12α‐epoxy‐urs‐20(30)‐en‐28,13β‐olide, xerophilusin B, and 15α‐hydroxy‐6,7‐seco‐1α,7:11α,6‐diolide‐ent‐kaur‐16‐en, they exhibited low toxicity and safety for oral administration. Hence, these compounds may serve as potential candidates to replace the inhibitor SPD‐304 as important therapeutic agents against TNF‐α in the future. The results obtained need to be further investigated through in‐depth in vitroand in vivoexperiment studies.

Morinda longissimaY. Z. Ruan (“Nhó đông") belongs to the Rubiaceae family. In Vietnam, the stems and roots of this plant are commonly used to treat liver diseases, such as viral hepatitis and acute and chronic cirrhosis. A phytochemical study of this hepatoprotective plant revealed the presence of 21 natural compounds of different classes, including iridoids, naphthalene glycosides, and especially anthraquinones and anthraquinone glycosides. The primary goal of this study was to investigate the anti‐inflammatory potential of bioactive molecules from M. longissimatargeted against TNF‐αusing a molecular docking approach. The results revealed that two anthraquinone glycosides, morindone‐6‐O‐β‐gentiobioside (1) and lucidin‐3‐O‐β‐primeveroside (2), had good binding affinities (∆G values of ‐9.21 and ‐8.75 kcal/mol, respectively), better than that of the TNF‐αinhibitor, SPD‐304 (‐8.71 kcal/mol). The in silicoADME parameters of (1) and (2) and other compounds showed good bioavailability based on their absorption, distribution, metabolism, and excretion parameters. In addition, the oral toxicity of these compounds was determined to be low and safe. All this evidence showed it is worth further study and the development of potential anthraquinone glycosides from M. longissimaroots as TNF‐αnatural inhibitors for the treatment of inflammatory diseases such as rheumatoid arthritis, sclerosis, and hepatitis.