Sinomenine is an isoquinoline alkaloid isolated from Qingfeng vine, a traditional Chinese medicine for the treatment of rheumatic diseases. In recent years, scholars at home and abroad have conducted in-depth research on its pharmacological effects, and found that it has anti-inflammatory, immune, analgesic, antihypertensive, anti-arrhythmic and other physiological activities. Clinically, its hydrochloride preparation is commonly used for the treatment of rheumatoid arthritis and arrhythmia, and has achieved good therapeutic effects.
Pharmacological effects of Sinomenine
(1) Effect on the cardiovascular system
Sinomenine can affect heart function and has obvious anti-arrhythmic effects, and experiments have confirmed that Sinomenine can prolong LVET and QS2 during cardiac contraction in rabbits, and it is a blood concentration-dependent trend. The experimental results showed that Sinomenine had the effect of inhibiting the transmembrane current of Na+ and K+. The results of patch-clamp whole-cell recording showed that Sinomenine had concentration- and frequency-dependent blocking effects on INa and concentration-dependent blocking effect on Ca-L.
(2) Effect on the central nervous system
Sinomenine has a significant stabilizing effect. Sinomenine can significantly inhibit the spontaneous activity and passive activity of animals, manifested as reduced activity, quiet, drooping eyelids, animal experimental studies have found that Sinomenine has a good effect on large, mouse opioid-dependent withdrawal symptoms, the inhibitory activity of enkephalin receptors is more than 75%, and it is not addictive. Qingfeng vine can produce obvious inhibitory and blocking effects on the inhibition and blocking effect of morphine-dependent isolated guinea pig ileum, and the higher the dose, the more obvious the inhibitory effect. It can significantly reduce the urge withdrawal symptoms and weight loss in morphine-dependent mice; Sinomenine can eliminate the conditional position preference for morphine production, and its mechanism of action is related to the reduction of central cAMP levels. It can also regulate the disorder of neurotransmitter levels in the brain of morphine-dependent rats, and reduce the sudden increase of monoamine neurotransmitters after withdrawal. These studies suggest that Sinomenine can be used not only for the treatment of opioid withdrawal symptoms, but also for the treatment of other drug dependence.
(3) Anti-inflammatory effect
Sinomenine has anti-inflammatory effects on chemical, proteinic, and bacterial inflammation, and Sinomenine tablets with Sinomenine as the main component can significantly reduce the number of twists in mice, and there is a good correlation between dose and inhibition rate. Sinomenine has obvious analgesic effect on experimental mice, and the mechanism may be that Sinomenine has the effect of inhibiting the synthesis and release of local PGE in inflammation. The therapeutic effect of Sinomenine on adjuvant arthritis and the effect of nitric oxide and related inflammatory mediators in the secondary validation area showed that the therapeutic effect of Sinomenine rheumatoid arthritis was related to its inhibition of cytokine activity in the local area of inflammation and the reduction of inflammatory mediator content, and the reduction of NO level by Sinomenine may be an important mechanism of anti-rheumatoid arthritis.
Synthesis and structural modification of Sinomenine derivatives
Sinomenine has low bioavailability and is rapidly metabolized in the body, resulting in its inability to exert its efficacy in time. Therefore, in recent years, the structure of Sinomenine has been modified and optimized, and the derivatives synthesized by structural modification have been studied more. Sinomenine is composed of hydrophenanthrene nucleus and ethylamine bridge, which is similar in structure to morphine and codeine, and its structure is shown in the figure below. The Sinomenine skeleton is composed of four rings: A, B, C, and D, wherein A ring is a benzene ring, B ring is a semi-chair six-membered ring connected to a ring, C ring is a twisted chair six-membered ring with a α and β unsaturated ketone structure connec...
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