1. Description
Leonurine hydrochloride is a natural alkaloid derived from the Lamiaceae plant Leonurus japonicus. It is the characteristic active component and primary pharmacologically active substance of this plant. Its chemical structure is the hydrochloride salt of 3,5-dimethoxy-4-hydroxybenzoic acid (4-guanidino)-1-butyl ester. It appears as a powder and is soluble in cold water; its monohydrate form has a melting point of 193–194°C (decomposition). Pharmacokinetic studies indicate that this compound is widely distributed in the body, primarily in the stomach, liver, kidneys, lungs, spleen, heart, and pancreas. It does not readily cross the blood-brain barrier, has a plasma protein binding rate of less than 80%, and an oral bioavailability of approximately 2.21%, suggesting a significant first-pass effect.
2. Application
(1) Cardiovascular system research: Used in studies on anti-myocardial ischemia, anti-atherosclerosis, and cardiovascular protection. Research indicates that it can reduce the area of vascular plaques and inflammation through mechanisms such as regulating lipid metabolism, inhibiting macrophage foam cell formation, and activating cellular autophagy.
(2) Gynecological Disease Research: Used in studies on uterine function regulation and related diseases, including the regulation of uterine smooth muscle contractility, protection of ovarian function, and improvement of premature ovarian insufficiency. In drug-induced ovarian injury models, it protects ovarian function by inhibiting the NLRP3/GSDMD-mediated pyroptosis pathway.
(3) Skeletal System Research: Used in osteoporosis research, it reduces estrogen-deficient bone loss by inhibiting RANKL-induced osteoclastogenesis. Its mechanism of action involves inhibiting RANK-TRAF6 binding and downstream NF-κB and PI3K/Akt signaling pathways.
(4) Nervous System Research: Used in neuroprotective studies; however, it does not readily cross the blood-brain barrier, so its applications primarily focus on its anti-inflammatory and antioxidant activities.
(5) Digestive System Research: Used in studies of intestinal inflammation and barrier function. In endotoxin-induced models, it can alleviate intestinal inflammatory responses and protect intestinal barrier integrity by inhibiting the NF-κB/MAPK signaling pathway.
3. Main Efficacy
(1) Regulation of uterine contractions: It stimulates uterine smooth muscle, increasing the amplitude of uterine contractions, with effects lasting for several hours. It exerts a dose-dependent, bidirectional regulatory effect on the spontaneously contracting uterus. Additionally, in a model of premature ovarian insufficiency, it protects fertility by maintaining serum hormone levels and follicle count.
(2) Cardiovascular protective effects: It exerts anti-myocardial ischemia effects, inhibiting ECG T-wave changes and reducing serum malondialdehyde levels and lactate dehydrogenase activity. By activating METTL3-mediated regulation of AKT1S1 mRNA stability, it promotes foam cell autophagy and metabolic remodeling, thereby improving atherosclerosis. At low doses, it enhances contractility of isolated frog hearts; intravenous administration produces a transient hypotensive effect.
(3) Anti-inflammatory and antioxidant effects: In macrophages and chondrocytes, it inhibits the expression of pro-inflammatory factors such as iNOS, COX-2, TNF-α, and IL-6 induced by lipopolysaccharide or IL-1β. It alleviates inflammatory responses by inhibiting the NF-κB and MAPK signaling pathways. It also possesses antioxidant activity, reducing levels of lipid peroxides.
(4) Regulation of Bone Metabolism: It reduces bone resorption by inhibiting osteoclast formation and actin ring formation. In estrogen-deficient osteoporosis models, it prevents bone loss.
(5) Cell Protection and Metabolic Regulation: It protects against free fatty acid-induced hepatocyte damage, reduces intracellular lipid accumulation, and improves lipid metabolism. It exerts these effects by activating the AMPK/SREBP1 pathway. It regulates the expression of ABCA1 and ABCG1, genes associated with cholesterol efflux.
(6) Antitumor and Angiogenic Effects: It exhibits antitumor activity and promotes angiogenesis, and demonstrates the ability to regulate apoptosis in various disease models.
