Integrated network pharmacology and therapeutic verification of Dendrobium officinale flower on primary dysmenorrhea via inhibition of the TLR4/NF-κB/COX-2 pathway

  • Fitoterapia. 2025 Oct 6:187:106924. doi: 10.1016/j.fitote.2025.106924.
Manman Li  1 ,  Pei Sheng  2 ,  Weiqing Shi  3 ,  Weiguang Li  4 ,  Luqian Li  5 ,  Xue Wang  5 ,  Haixia Wu  5 ,  Yuxin Wang  1 ,  Xiaofei An  6 ,  Lei Wang  7 ,  Ming Yan  8
Affiliations
  • 1. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China.
  • 2. Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210009, Jiangsu Province, China.
  • 3. Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China. Electronic address: [email protected].
  • 4. School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China.
  • 5. New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China.
  • 6. Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210009, Jiangsu Province, China. Electronic address: [email protected].
  • 7. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China. Electronic address: [email protected].
  • 8. New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China. Electronic address: [email protected].
PMID: 41061996 DOI: 10.1016/j.fitote.2025.106924
Abstract

Dendrobium officinale flowers (DOF) offer a wide range of therapeutic benefits due to their rich content of bioactive compounds. Traditionally used in Chinese medicine, these flowers are valued for their health benefits, including anti-inflammatory and antioxidant properties, which may contribute to their therapeutic effects. The anti-inflammatory and antioxidant extract of DOF exhibited anti-primary dysmenorrhea (PD) activity in oxytocin-induced mice. This study aimed to unravel the underlying mechanisms of DOF-EA in treating PD using an integrative approach that combines network pharmacology and experimental verification. The active fraction, DOF-EA, was identified through anti-inflammatory and antioxidant activity assays. The phytochemical profile of DOF-EA was characterized by HPLC analysis. The therapeutic mechanisms of DOF-EA in treating PD were predicted using network pharmacology and molecular docking analyses. Moreover, the therapeutic effects of DOF-EA were confirmed using oxytocin-induced mice and uterine strip models. Enzyme activity assays and immunoblotting methods were employed for target validation. DOF-EA inhibited COX-2 with an IC50 of 0.44 μg/mL, scavenged DPPH radicals with an IC50 of 9.88 μg/mL, and suppressed NO production in RAW 264.7 cells with an IC50 of 8.08 μg/mL. Additionally, DOF-EA reduced the writhing response and decreased TNF-α and PGF2α levels in PD mice. It also inhibited contraction activity in uterine strips by blocking calcium channels. Furthermore, DOF-EA downregulated the expression of TLR4, NF-κB, COX-2, and p-IκBα, while upregulating the expression of HO-1 and Nrf2 in the uterine tissue of PD mice. In conclusion, DOF-EA exerts therapeutic effects against PD by inhibiting TLR4/NF-κB/COX-2 and promoting the Nrf2/HO-1 pathway.

Keywords
COX-2; Dendrobium officinale flowers; NF-κB; Network pharmacology; Primary dysmenorrhea; TLR4.
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