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

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

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: shiwq@jscdc.cn.
  • 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: anxiaofei2000@163.com.
  • 7 School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China. Electronic address: wanglei@cpu.edu.cn.
  • 8 New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China. Electronic address: brookming@cpu.edu.cn.
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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