益母草經由低氧適應與抗細胞凋亡機制，恢復逼尿肌功能低下症之膀胱收縮力

LEONURUS JAPONICUS RESTORES BLADDER CONTRACTILITY IN DETRUSOR UNDERACTIVITY VIA HYPOXIA ADAPTATION AND ANTI-APOPTOTIC MECHANISMS

黃偉柏, 林健煇, 何東儒, 黃雲慶, 陳志碩, 林威宇

嘉義長庚紀念醫院外科部泌尿科

Wei Po, Huang¹, Jian-Hui Lin¹, Dong-Ru Ho¹, Yun-Chin Huang¹, Chih-Shou Chen, Wei-Yu Lin

1 Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan, Chia Yi, Taiwan

Purpose:

Detrusor underactivity (DU) is increasingly prevalent in aging populations and is characterized by impaired bladder contractility and inefficient voiding. Current pharmacological treatments, primarily targeting parasympathetic pathways, show limited efficacy. Leonurus japonicus, a traditional herbal medicine with established protective effects against ischemia-reperfusion injury, may offer therapeutic benefit through mechanisms related to hypoxic adaptation. This study aimed to investigate the therapeutic potential and underlying mechanisms of Leonurus japonicus extract (LJE) in both cellular and animal models of DU.

Methods:

Human bladder smooth muscle cells were subjected to hypoxia for 24 hours and treated with LJE (0, 5, 10 μg/μl). Protein expression of hypoxia-related markers (HIF-1α, iNOS), apoptosis (Bax, BCL-2, cleaved caspase-3), inflammation (NF-κB, TNF-α), and fibrosis (TGF-β1) was analyzed by Western blot.

In vivo, a rat partial bladder ischemia (PIB) model was used. Animals were divided into four groups: sham control, DU, DU+LJE, and DU+LJE+tolterodine (n=8 each). Urodynamic parameters including maximum voiding pressure (Pmax), inter-contraction interval (ICI), and voiding time (Vt) were measured at 4 weeks.

Results:

LJE enhanced hypoxia adaptation, with increased HIF-1α and iNOS expression. It significantly reduced apoptotic markers (Bax, cleaved caspase-3), inflammatory mediators (NF-κB, TNF-α), and fibrosis marker TGF-β1.

In vivo, PIB significantly impaired bladder contractility. LJE monotherapy restored contractile function and improved Pmax beyond control levels, whereas combination therapy with tolterodine showed less pronounced improvement. Both treatment groups demonstrated normalization of voiding time.

Conclusions:

Leonurus japonicus exerts multi-target therapeutic effects in DU by enhancing hypoxia adaptation, suppressing apoptosis, and reducing inflammation and fibrosis. Its superior efficacy as monotherapy suggests a novel ischemia-targeted therapeutic strategy distinct from conventional antimuscarinic approaches. Further clinical studies are warranted.