Effects of Schisandra chinensis extract on the contractility of corpus cavernosal smooth muscle (CSM) and Ca2+ homeostasis in CSM cells

• Published in: BJU international Vol. 109; no. 9; pp. 1404 - 1413
• Main Authors: Han, Deok Hyun, Lee, Jun Ho, Kim, Hyunjung, Ko, Mi Kyeong, Chae, Mee Ree, Kim, Hye Kyung, So, Insuk, Jeon, Ju‐Hong, Park, Jong Kwan, Lee, Sung Won
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-05-2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Animals; Biological and medical sciences; Dose-Response Relationship, Drug; Endothelium; erectile dysfunction; Fluorescent Dyes; Fruit - chemistry; Fura-2; Gynecology. Andrology. Obstetrics; In Vitro Techniques; Male; Male genital diseases; Medical sciences; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Nephrology. Urinary tract diseases; NMR; Non tumoral diseases; Nuclear magnetic resonance; Patch-Clamp Techniques; Penis - drug effects; Plant Extracts - pharmacology; potassium channels; Potassium Channels, Calcium-Activated - drug effects; Potassium Channels, Inwardly Rectifying - drug effects; Rabbits; Schisandra; Schisandra - chemistry; Schisandra chinensis; Smooth muscle; smooth muscle cell; Studies; transient receptor potential channels; TRPC Cation Channels - drug effects; Nephrology; smooth muscle cell; Calcium; Erection disorders; Impotence; Sexual dysfunction; Contractility; Homeostasis; Smooth muscle; Ionic channel; Corpus cavernosum; Extract; transient receptor potential channels; Inorganic element; Transitory; Urology; Myocyte; erectile dysfunction; Calcium ion; Schisandra chinensis; potassium channels; Male genital diseases; Potassium; Biological receptor
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2011.10567.x

What's known on the subject? and What does the study add?
Schisandra chinensis extract (SCE) has been known to have relaxative effects on penile smooth muscle. A recent study showed that SCE could enhance slidenafil citrate‐induced relaxation of penile corpus cavernosum.
The current study investigated the mechanism of action of SCE and its constituents on corporal smooth muscle cells. And this study shows that SCE induced relaxation of CSM primarily through an endothelium independent pathway and the relaxation effects of SCE on corporal smooth muscle are, in part, due to the activation of K+ channels and inhibition of TRPC6 channels, resulting in decreased [Ca2+].
OBJECTIVE
• 
To evaluate the relaxant effects of Schisandra chinensis extract (SCE) on corporal tissue in the penis and to investigate the mechanism of action of SCE and its constituents on corporal smooth muscle (CSM) cells.
MATERIALS AND METHODS
• 
The fruit of SC was collected and extracted with ethanol. Six SC lignans (schisandrol A, schisandrol B, schisandrin A, schisandrin B, gomisin N, and schisandrin C) were isolated and purified, and the chemical structures were confirmed by 1H‐nuclear magnetic resonance (NMR) and 13C‐NMR data.
• 
Isolated rabbit CSM strips were mounted in an organ‐bath system, and the effects of SCE were evaluated.
• 
To estimate the intracellular Ca2+ level ([Ca2+]i), we used a Fura‐2 fluorescent technique, and a conventional whole‐cell patch‐clamp technique was used to measure the calcium‐sensitive K+ channels (KCa), inward rectifier K+ channels (KIR), and canonical transient receptor potential cation channel 6 (TRPC6) currents.
RESULTS
• 
SCE induced concentration‐dependent relaxation in contracted CSM tissue, and the removal of the endothelium did not significantly affect their relaxation potencies.
• 
In CSM cells, extracellular application of SCE significantly increased whole‐cell KCa currents (117.4%) and KIR currents (110.0%). These effects were completely abolished by charybdotoxin or BaCl2.
• 
In contrast, carbachol‐induced TRPC6 channel activity was significantly inhibited (87.3%) by SCE in green fluorescent protein‐TRPC6 pcDNA transfected HEK 293 cells. [Ca2+]i measurements showed that SCE effectively reduced basal [Ca2+]i in both cell lines (CSM cells and A7r5 cells) and the [Arg8]‐vasopressin (AVP)‐induced [Ca2+]i increase in A7r5 cells.
• 
Among the six SC lignans, schisandrin A and schisandrin B most effectively attenuated the AVP‐induced [Ca2+]i increase.
CONCLUSIONS
• 
SCE induced relaxation of CSM that occurred primarily via an endothelium‐independent pathway.
• 
The relaxation effects of SCE on CSM were, in part, due to the activation of K+ channels and inhibition of TRPC6 channels, resulting in decreased [Ca2+]i.